Change in schistosome sex ratio under the influence of a biotic environmental-related factor.

Science.gov (United States)

Moné, H

1997-04-01

Schistosoma mansoni is a dioecious trematode responsible for intestinal schistosomiasis in man. The sex ratio was determined for S. mansoni adults derived from cercariae obtained from infected Biomphalaria glabrata maintained in the presence of the nonvector molluse. Marisa cornuarietis. The presence of M. cornuarietis is responsible for enhanced growth of B. glabrata and for a change in the sex ratio of the schistosome, which becomes more male-biased as compared to control snails maintained in aquaria lacking M. cornuarietis. This is the first time the presence of another species in the environment has been shown to influence schistosome sex ratios. Two nonexclusive hypotheses are proposed to explain this variation in the sex ratio: sexual competition between male and female sporocysts; and sex reversal.

β5i subunit deficiency of the immunoproteasome leads to reduced Th2 response in OVA induced acute asthma.

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Anton Volkov

Full Text Available The immunoproteasome subunit β5i has been shown to play an important role in Th1/Th17 driven models of colitis and arthritis. However, the function of β5i in Th2 dependent diseases remains enigmatic. To study the role of β5i in Th2-driven pathology, β5i knockout (KO and control mice were tested in different models of experimental allergic asthma. β5i-deficient mice showed reduced OVA/Alum- and subcutaneous/OVA-induced acute asthma with decreased eosinophilia in the bronchoalveolar lavage (BAL, low OVA-specific IgG1 and reduced local and systemic Th2 cytokines. While Th2 cells in the lungs were reduced, Tregs and Th1 cells were not affected. Attenuated asthma in β5i KO mice could not be attributed to defects in OVA uptake or maturation of dendritic cells in the lung. Surprisingly, β5i deficient mice developed HDM asthma which was comparable to control mice. Here, we present novel evidence for the requirement of the β5i immunosubunit to generate a strong Th2 response during OVA- but not HDM-induced acute asthma. The unexpected role of β5i in OVA asthma remains to be clarified.

No apparent reduction in schistosome burden or genetic diversity following four years of school-based mass drug administration in mwea, central kenya, a heavy transmission area.

Science.gov (United States)

Lelo, Agola E; Mburu, David N; Magoma, Gabriel N; Mungai, Ben N; Kihara, Jimmy H; Mwangi, Ibrahim N; Maina, Geoffrey M; Kinuthia, Joseph M; Mutuku, Martin W; Loker, Eric S; Mkoji, Gerald M; Steinauer, Michelle L

2014-10-01

Schistosomiasis is a debilitating neglected tropical disease that infects over 200 million people worldwide. To combat this disease, in 2012, the World Health Organization announced a goal of reducing and eliminating transmission of schistosomes. Current control focuses primarily on mass drug administration (MDA). Therefore, we monitored transmission of Schistosoma mansoni via fecal egg counts and genetic markers in a typical school based MDA setting to ascertain the actual impacts of MDA on the targeted schistosome population. For 4 years, we followed 67 children enrolled in a MDA program in Kenya. Infection status and egg counts were measured each year prior to treatment. For 15 of these children, for which there was no evidence of acquired resistance, meaning they became re-infected following each treatment, we collected microsatellite genotype data from schistosomes passed in fecal samples as a representation of the force of transmission between drug treatments. We genotyped a total of 4938 parasites from these children, with an average of 329.2 parasites per child for the entire study, and an average of 82.3 parasites per child per annual examination. We compared prevalence, egg counts, and genetic measures including allelic richness, gene diversity (expected heterozygosity), adult worm burdens and effective number of breeders among time points to search for evidence for a change in transmission or schistosome populations during the MDA program. We found no evidence of reduced transmission or schistosome population decline over the course of the program. Although prevalence declined in the 67 children as it did in the overall program, reinfection rates were high, and for the 15 children studied in detail, schistosome egg counts and estimated adult worm burdens did not decline between years 1 and 4, and genetic diversity increased over the course of drug treatment. School based control programs undoubtedly improve the health of individuals; however, our data

c-KIT positive schistosomal urinary bladder carcinoma are frequent but lack KIT gene mutations.

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Shams, Tahany M; Metawea, Mokhtar; Salim, Elsayed I

2013-01-01

Urinary bladder squamous cell carcinoma (SCC), one of the most common neoplasms in Egypt, is attributed to chronic urinary infection with Schistosoma haematobium (Schistosomiasis). The proto-oncogene c-KIT, encoding a tyrosine kinase receptor and implicated in the development of a number of human malignancies, has not been studied so far in schistosomal urinary bladder SCCs. We therefore determined immunohistochemical (IHC) expression of c-KIT in paraffin sections from 120 radical cystectomies of SCCs originally obtained from the Pathology Department of Suez Canal University (Ismailia, Egypt). Each slide was evaluated for staining intensity where the staining extent of >10% of cells was considered positive. c-KIT overexpression was detected in 78.3% (94/120) of the patients, the staining extents in the tumor cells were 11-50% and >50% in 40 (42.6%) and 54 (57.4%) respectively. The positive cases had 14.9%, 63.8%, 21.3% as weak, moderate and strong intensity respectively. Patients with positive bilharzial ova had significantly higher c-KIT expression than patients without (95.2% vs. 38.9%, P=0.000). Mutation analysis of exons 9-13 was negative in thirty KIT positive cases. The high rate of positivity in SBSCC was one of the striking findings; However, CD117 may be a potential target for site specific immunotherapy to improve the outcome of this tumor.

Schistosome serine protease inhibitors: parasite defense or homeostasis?

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Landys A. Lopez Quezada

2011-06-01

Full Text Available Serpins are a structurally conserved family of macromolecular inhibitors found in numerous biological systems. The completion and annotation of the genomes of Schistosoma mansoni and Schistosoma japonicum has enabled the identification by phylogenetic analysis of two major serpin clades. S. mansoni shows a greater multiplicity of serpin genes, perhaps reflecting adaptation to infection of a human host. Putative targets of schistosome serpins can be predicted from the sequence of the reactive center loop (RCL. Schistosome serpins may play important roles in both post-translational regulation of schistosome-derived proteases, as well as parasite defense mechanisms against the action of host proteases.Serpinas são uma família de inibidores macromoleculares estruturalmente conservados encontrados em inúmeros sistemas biológicos. O término e a anotação dos genomas de Schistosoma mansoni e de Schistosoma japonicum permitiram a identificação por análise filogenética de dois principais clados de serpinas. S. mansoni mostra uma multiplicidade maior de genes de serpinas, talvez refletindo uma adaptação à infecção de um hospedeiro humano. Alvos putativos das serpinas de esquistossomos podem ser preditos a partir da sequência do "loop" do centro reativo. Serpinas de esquistossomos podem ter importantes papeis tanto na regulação pós-traducional de proteases derivadas do esquistossoma, quanto nos mecanismos de defesa contra a ação de proteases do hospedeiro.

Trans Ova Genetics, L.C. - Clean Water Act Public Notice

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The EPA is providing notice of a proposed Administrative Penalty Assessment against Trans Ova Genetics, L.C., a business located at 2938 380th Street Sioux Center, IA 51250, for alleged violations at the Trans Ova Genetics, L.C.’s facility located in 12425

[Effect of Parasep® feces centrifuge tube method on detecting schistosome eggs].

Science.gov (United States)

Ma, Nian; Zhang, Hua-ming; Liu, Xiong; Xiao, Chuan-yun; Wen, Xiao-hong; Li, Xia; Dong, Li-chun; Cui, Cai-xia; Tu, Zu-wu

2014-08-01

To evaluate the effect of the Parasep® feces centrifuge tube method on detecting schistosome eggs. A total of 803 residents aged from 6-65 years were selected in 2 schistosomiasis endemic villages, Jiangling County, Hubei Province, and their stool samples were collected and detected parallelly by the Kato-Katz technique, nylon silk egg hatching method, and Parasep® feces centrifuge tube method at the same time. Among the 803 people, 15 cases were found of schistosome egg positive, and the positive rate was 1.87%. The positive rates of the Kato-Katz technique, nylon silk egg hatching method, and Parasep® feces centrifuge tube method were 0.75%, 1.49% and 1.12%, respectively. The schistosome eggs got with the Parasep® feces centrifuge tube method were clear and easy to identify. In low endemic areas of schistosomiasis, the Parasep® feces centrifuge tube method can be used as schistosomiasis japonica etiology diagnosis method.

Host immunity, nutrition and coinfection alter longitudinal infection patterns of schistosomes in a free ranging African buffalo population.

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Brianna R Beechler

2017-12-01

Full Text Available Schistosomes are trematode parasites of global importance, causing infections in millions of people, livestock, and wildlife. Most studies on schistosomiasis, involve human subjects; as such, there is a paucity of longitudinal studies investigating parasite dynamics in the absence of intervention. As a consequence, despite decades of research on schistosomiasis, our understanding of its ecology in natural host populations is centered around how environmental exposure and acquired immunity influence acquisition of parasites, while very little is known about the influence of host physiology, coinfection and clearance in the absence of drug treatment. We used a 4-year study in free-ranging African buffalo to investigate natural schistosome dynamics. We asked (i what are the spatial and temporal patterns of schistosome infections; (ii how do parasite burdens vary over time within individual hosts; and (iii what host factors (immunological, physiological, co-infection and environmental factors (season, location explain patterns of schistosome acquisition and loss in buffalo? Schistosome infections were common among buffalo. Microgeographic structure explained some variation in parasite burdens among hosts, indicating transmission hotspots. Overall, parasite burdens ratcheted up over time; however, gains in schistosome abundance in the dry season were partially offset by losses in the wet season, with some hosts demonstrating complete clearance of infection. Variation among buffalo in schistosome loss was associated with immunologic and nutritional factors, as well as co-infection by the gastrointestinal helminth Cooperia fuelleborni. Our results demonstrate that schistosome infections are surprisingly dynamic in a free-living mammalian host population, and point to a role for host factors in driving variation in parasite clearance, but not parasite acquisition which is driven by seasonal changes and spatial habitat utilization. Our study illustrates

SCHISTOSOMAL APPENDICITIS IN A SLIDING HERNIA (CASE ...

African Journals Online (AJOL)

We report a rare case of a forty-seven year old Nigeria male with schistosomal appendicitis in a sliding hernia. The clinical and pathological features of the case are discussed, followed by a review of the literature. It is concluded that a high index of suspicion is necessary to diagnose unusual presentations of ...

Dynamics of paediatric urogenital schistosome infection, morbidity and treatment: a longitudinal study among preschool children in Zimbabwe.

Science.gov (United States)

Osakunor, Derick Nii Mensah; Mduluza, Takafira; Midzi, Nicholas; Chase-Topping, Margo; Mutsaka-Makuvaza, Masceline Jenipher; Chimponda, Theresa; Eyoh, Enwono; Mduluza, Tariro; Pfavayi, Lorraine Tsitsi; Wami, Welcome Mkululi; Amanfo, Seth Appiah; Murray, Janice; Tshuma, Clement; Woolhouse, Mark Edward John; Mutapi, Francisca

2018-01-01

inclusion of PSAC in schistosome control programmes.

Aerobic Exercise Decreases Lung Inflammation by IgE Decrement in an OVA Mice Model.

Science.gov (United States)

Camargo Hizume-Kunzler, Deborah; Greiffo, Flavia R; Fortkamp, Bárbara; Ribeiro Freitas, Gabriel; Keller Nascimento, Juliana; Regina Bruggemann, Thayse; Melo Avila, Leonardo; Perini, Adenir; Bobinski, Franciane; Duarte Silva, Morgana; Rocha Lapa, Fernanda; Paula Vieira, Rodolfo; Vargas Horewicz, Verônica; Soares Dos Santos, Adair Roberto; Cattelan Bonorino, Kelly

2017-06-01

Aerobic exercise (AE) reduces lung function decline and risk of exacerbations in asthmatic patients. However, the inflammatory lung response involved in exercise during the sensitization remains unclear. Therefore, we evaluated the effects of exercise for 2 weeks in an experimental model of sensitization and single ovalbumin-challenge. Mice were divided into 4 groups: mice non-sensitized and not submitted to exercise (Sedentary, n=10); mice non-sensitized and submitted to exercise (Exercise, n=10); mice sensitized and exposed to ovalbumin (OVA, n=10); and mice sensitized, submitted to exercise and exposed to OVA (OVA+Exercise, n=10). 24 h after the OVA/saline exposure, we counted inflammatory cells from bronchoalveolar fluid (BALF), lung levels of total IgE, IL-4, IL-5, IL-10 and IL-1ra, measurements of OVA-specific IgG1 and IgE, and VEGF and NOS-2 expression via western blotting. AE reduced cell counts from BALF in the OVA group (p<0.05), total IgE, IL-4 and IL-5 lung levels and OVA-specific IgE and IgG1 titers (p<0.05). There was an increase of NOS-2 expression, IL-10 and IL-1ra lung levels in the OVA groups (p<0.05). Our results showed that AE attenuated the acute lung inflammation, suggesting immunomodulatory properties on the sensitization process in the early phases of antigen presentation in asthma. © Georg Thieme Verlag KG Stuttgart · New York.

Immunological Consequences of Antihelminthic Treatment in Preschool Children Exposed to Urogenital Schistosome Infection

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Nadine Rujeni

2013-01-01

Full Text Available Urogenital schistosomiasis, due to Schistosoma haematobium, is endemic in sub-Saharan Africa. Control is by targeted treatment with praziquantel but preschool age children are excluded from control programs. Immunological studies on the effect of treatment at this young age are scarce. In light of studies in older individuals showing that praziquantel alters antischistosome immune responses and responses to bystander antigens, this study aims to investigate how these responses would be affected by treatment at this young age. Antibody responses directed against schistosome antigens, Plasmodium falciparum crude and recombinant antigens, and the allergen house dust mite were measured in children aged 3 to 5 years before and 6 weeks after treatment. The change in serological recognition of schistosome proteins was also investigated. Treatment augmented antischistosome IgM and IgE responses. The increase in IgE responses directed against adult worm antigens was accompanied by enhanced antigen recognition by sera from the children. Antibody responses directed against Plasmodium antigens were not significantly affected by praziquantel treatment nor were levels of allergen specific responses. Overall, praziquantel treatment enhanced, quantitatively and qualitatively, the antiworm responses associated with protective immunity but did not alter Plasmodium-specific responses or allergen-specific responses which mediate pathology in allergic disease.

Presence of parasitic ova, cysts and larva on common fresh fruits ...

African Journals Online (AJOL)

Several parasitic infections are associated with poor hygiene and environmental sanitation resulting in food and water containing ova, cysts or larva of these parasites. Therefore, a survey of fruits and vegetables sold at some major markets in Ibadan was carried out between January and June, 2011 to identify the ova, cyst ...

Molecular diversity of avian schistosomes in Danish freshwater snails

DEFF Research Database (Denmark)

Christiansen, Anne Ø.; Olsen, Annette; Buchmann, Kurt

2016-01-01

Avian schistosomes are widespread parasites of snails and waterfowl and may cause cercarial dermatitis (swimmer's itch) in humans, a disease that is frequently reported in European countries. These parasites are known to occur in Denmark, but here, we applied a new approach using molecular tools ...

Morphological Specifications of the Bird Schistosome Cercariae and Surface Carbohydrates as Receptors for Lectins

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I Moebedi

2007-04-01

Full Text Available Background: To determine the morphological specifications of the bird schistosomes cercaria from Lymnaea gedrosiana and to detect the surface carbohydrates as receptors for host lectins in the host-parasite relationship systems such as avian schistosomiasis and human cercarial dermatitis. Methods: One hundred ninety two snails collected from Dezful areas in Khuzestan Province, in the south west of Iran, during 2005-2006 were examined for cercariae using shedding and crushing methods. In addition, surface carbohydrates on the cercariae were detected by lentil (Lens culinaris lectins. Results: From the total number of Lymnaea gedrosiana, which examined for bird schistosomes cercaria, 9(4% snails were found to be infected with furcocercus cercaria of the bird schistosomes (probably Gigantobilharzia sp.. Mannose monosaccharide CH2OH (CHOH4CHO as surface carbohydrate was also detected on the cercariae. Conclusion: Mannose carbohydrate on these cercariae may be used as receptor by lectins.

OVA-specific CD8(+)T cells do not express granzyme B during anterior chamber associated immune deviation

NARCIS (Netherlands)

Ren, Y.; Yang, P.; Li, B.; Gao, Y.; Zhou, H.; Huang, X.; Zhu, L.; Kijlstra, A.

2006-01-01

To examine antigen (Ag)-specific CTL response during anterior chamber associated immune deviation (ACAID). Methods OVA or OVA257-264 peptide was injected into the anterior chamber (AC) of C57BL/6 mice. There were 16 mice in each ACAID group induced with OVA or OVA257-264 peptide. The mice were

Molecular Detection of Schistosome Infections with a Disposable Microfluidic Cassette.

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Jinzhao Song

2015-12-01

Full Text Available Parasitic helminths such as schistosomes, as well as filarial and soil-transmitted nematodes, are estimated to infect at least a billion people worldwide, with devastating impacts on human health and economic development. Diagnosis and monitoring of infection dynamics and efficacy of treatment depend almost entirely on methods that are inaccurate, labor-intensive, and unreliable. These shortcomings are amplified and take on added significance in mass drug administration programs, where measures of effectiveness depend on accurate monitoring of treatment success (or failure, changes in disease transmission rates, and emergence of possible drug resistance. Here, we adapt isothermal molecular assays such as loop-mediated isothermal amplification (LAMP to a simple, hand-held, custom-made field-ready microfluidic device that allows sensitive and specific detection of schistosome cell-free nucleic acids in serum and plasma (separated with a point-of-care plasma separator from Schistosoma mansoni-infected mice. Cell-free S. mansoni DNA was detected with our device without prior extraction from blood. Our chip exhibits high sensitivity (~2 x 10(-17 g/μL, with a positive signal for S. mansoni DNA detectable as early as one week post infection, several weeks before parasite egg production commences. These results indicate that incorporation of isothermal amplification strategies with our chips could represent a strategy for rapid, simple, low-cost diagnosis of both pre-patent and chronic schistosome infections as well as potential monitoring of treatment efficacy.

Nuclear techniques in schistosomiasis: Towards a schistosome vaccine

International Nuclear Information System (INIS)

Taylor, D.W.

1986-01-01

The paper reviews recent advances in schistosome research achieved through the application of nuclear techniques and aimed at the development of a vaccine. Two principal areas are discussed: first, immune effector mechanisms; and secondly, the application of hybridoma and recombinant DNA technology to the problem of production of large quantities of parasite antigens suitable for inclusion in an experimental vaccine. (author)

Schistosome infection intensity is inversely related to auto-reactive antibody levels.

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Francisca Mutapi

2011-05-01

Full Text Available In animal experimental models, parasitic helminth infections can protect the host from auto-immune diseases. We conducted a population-scale human study investigating the relationship between helminth parasitism and auto-reactive antibodies and the subsequent effect of anti-helminthic treatment on this relationship. Levels of antinuclear antibodies (ANA and plasma IL-10 were measured by enzyme linked immunosorbent assay in 613 Zimbabweans (aged 2-86 years naturally exposed to the blood fluke Schistosoma haematobium. ANA levels were related to schistosome infection intensity and systemic IL-10 levels. All participants were offered treatment with the anti-helminthic drug praziquantel and 102 treated schoolchildren (5-16 years were followed up 6 months post-antihelminthic treatment. ANA levels were inversely associated with current infection intensity but were independent of host age, sex and HIV status. Furthermore, after allowing for the confounding effects of schistosome infection intensity, ANA levels were inversely associated with systemic levels of IL-10. ANA levels increased significantly 6 months after anti-helminthic treatment. Our study shows that ANA levels are attenuated in helminth-infected humans and that anti-helminthic treatment of helminth-infected people can significantly increase ANA levels. The implications of these findings are relevant for understanding both the aetiology of immune disorders mediated by auto-reactive antibodies and in predicting the long-term consequences of large-scale schistosomiasis control programs.

Morphology and surface topography of the schistosome Bivitellobilharzia nairi from the Asian elephant (Elephas maximus maximus) in Sri Lanka.

Science.gov (United States)

Rajapakse, R P V J; Iwagami, M; Wickramasinghe, S; Walker, S M; Agatsuma, T

2013-09-01

Bivitellobilharzia nairi was first recorded from an Indian elephant (Elephas maximus) in Berlin. Infections with this parasite have become increasingly important in E. maximus maximus populations in Sri Lanka. The present work is the first morphological description of this schistosome from Sri Lanka. A number of adult worms were recovered from a dead Asian elephant near the elephant orphanage, Pinnawala, in Sri Lanka. The observed clinical features of the infected elephant included emaciation, subventral oedema and anaemia. Post-mortem results indicated that the liver was enlarged and adult schistosomes were found in the blood vessels of the liver parenchyma. The total number of worms recovered from a portion of the liver was 129,870, which is an average of 22 worms per 100 g of liver. The present study uses both light microscopic and scanning electron microscope (SEM) techniques for the morphological and topographical characterization of this parasite and to permit comparison with other species of schistosomes. Morphologically, these worms correspond very well to the description of B. nairi by Dutt & Srivastava (1955). Moreover, it is clear that B. nairi is a distinctive species easily differentiated from other schistosomes. The SEM study of the tegument of male worms shows that the surface of B. nairi is smoother than in other schistosomes.

Discovery and molecular characterization of a Bcl-2-regulated cell death pathway in schistosomes.

Science.gov (United States)

Lee, Erinna F; Clarke, Oliver B; Evangelista, Marco; Feng, Zhiping; Speed, Terence P; Tchoubrieva, Elissaveta B; Strasser, Andreas; Kalinna, Bernd H; Colman, Peter M; Fairlie, W Douglas

2011-04-26

Schistosomiasis is an infectious disease caused by parasites of the phylum platyhelminthe. Here, we describe the identification and characterization of a Bcl-2-regulated apoptosis pathway in Schistosoma japonicum and S. mansoni. Genomic, biochemical, and cell-based mechanistic studies provide evidence for a tripartite pathway, similar to that in humans including BH3-only proteins that are inhibited by prosurvival Bcl-2-like molecules, and Bax/Bak-like proteins that facilitate mitochondrial outer-membrane permeabilization. Because Bcl-2 proteins have been successfully targeted with "BH3 mimetic" drugs, particularly in the treatment of cancer, we investigated whether schistosome apoptosis pathways could provide targets for future antischistosomal drug discovery efforts. Accordingly, we showed that a schistosome prosurvival protein, sjA, binds ABT-737, a well-characterized BH3 mimetic. A crystal structure of sjA bound to a BH3 peptide provides direct evidence for the feasibility of developing BH3 mimetics to target Bcl-2 prosurvival proteins in schistosomes, suggesting an alternative application for this class of drugs beyond cancer treatment.

Cytokine responses to the anti-schistosome vaccine candidate antigen glutathione-S-transferase vary with host age and are boosted by praziquantel treatment.

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Claire D Bourke

2014-05-01

Full Text Available Improved helminth control is required to alleviate the global burden of schistosomiasis and schistosome-associated pathologies. Current control efforts rely on the anti-helminthic drug praziquantel (PZQ, which enhances immune responses to crude schistosome antigens but does not prevent re-infection. An anti-schistosome vaccine based on Schistosoma haematobium glutathione-S-transferase (GST is currently in Phase III clinical trials, but little is known about the immune responses directed against this antigen in humans naturally exposed to schistosomes or how these responses change following PZQ treatment.Blood samples from inhabitants of a Schistosoma haematobium-endemic area were incubated for 48 hours with or without GST before (n = 195 and six weeks after PZQ treatment (n = 107. Concentrations of cytokines associated with innate inflammatory (TNFα, IL-6, IL-8, type 1 (Th1; IFNγ, IL-2, IL-12p70, type 2 (IL-4, IL-5, IL-13, type 17 (IL-17A, IL-21, IL-23p19 and regulatory (IL-10 responses were quantified in culture supernatants via enzyme-linked immunosorbent assay (ELISA. Factor analysis and multidimensional scaling were used to analyse multiple cytokines simultaneously.A combination of GST-specific type 2 (IL-5 and IL-13 and regulatory (IL-10 cytokines was significantly lower in 10-12 year olds, the age group at which S. haematobium infection intensity and prevalence peak, than in 4-9 or 13+ year olds. Following PZQ treatment there was an increase in the number of participants producing detectable levels of GST-specific cytokines (TNFα, IL-6, IL-8, IFNγ, IL-12p70, IL-13 and IL-23p19 and also a shift in the GST-specific cytokine response towards a more pro-inflammatory phenotype than that observed before treatment. Participant age and pre-treatment infection status significantly influenced post-treatment cytokine profiles.In areas where schistosomiasis is endemic host age, schistosome infection status and PZQ treatment affect the

OVAS: an open-source variant analysis suite with inheritance modelling.

Science.gov (United States)

Mozere, Monika; Tekman, Mehmet; Kari, Jameela; Bockenhauer, Detlef; Kleta, Robert; Stanescu, Horia

2018-02-08

The advent of modern high-throughput genetics continually broadens the gap between the rising volume of sequencing data, and the tools required to process them. The need to pinpoint a small subset of functionally important variants has now shifted towards identifying the critical differences between normal variants and disease-causing ones. The ever-increasing reliance on cloud-based services for sequence analysis and the non-transparent methods they utilize has prompted the need for more in-situ services that can provide a safer and more accessible environment to process patient data, especially in circumstances where continuous internet usage is limited. To address these issues, we herein propose our standalone Open-source Variant Analysis Sequencing (OVAS) pipeline; consisting of three key stages of processing that pertain to the separate modes of annotation, filtering, and interpretation. Core annotation performs variant-mapping to gene-isoforms at the exon/intron level, append functional data pertaining the type of variant mutation, and determine hetero/homozygosity. An extensive inheritance-modelling module in conjunction with 11 other filtering components can be used in sequence ranging from single quality control to multi-file penetrance model specifics such as X-linked recessive or mosaicism. Depending on the type of interpretation required, additional annotation is performed to identify organ specificity through gene expression and protein domains. In the course of this paper we analysed an autosomal recessive case study. OVAS made effective use of the filtering modules to recapitulate the results of the study by identifying the prescribed compound-heterozygous disease pattern from exome-capture sequence input samples. OVAS is an offline open-source modular-driven analysis environment designed to annotate and extract useful variants from Variant Call Format (VCF) files, and process them under an inheritance context through a top-down filtering schema of

Evaluating the efficacy of a centrifugation-flotation method for extracting Ascaris ova from soil

DEFF Research Database (Denmark)

Cranston, Imogen; Teoh, Penelope J.; baker, Sarah M.

2016-01-01

method to extract STH ova from soil makes it challenging to examine whether the use of latrines may or may not have an effect on environmental contamination with ova. The present study evaluated the recovery rate of a method developed to extract STH ova from soil. Methods: The adapted centrifugation...... with increasing soil moisture content, particle size and organic matter content. The association between recovery rate and organic matter content was statistically significant. Conclusions: The present study identified a low recovery rate for an adapted centrifugation-flotation method, although this was similar...

Discovery and molecular characterization of a Bcl-2–regulated cell death pathway in schistosomes

Science.gov (United States)

Lee, Erinna F.; Clarke, Oliver B.; Evangelista, Marco; Feng, Zhiping; Speed, Terence P.; Tchoubrieva, Elissaveta B.; Strasser, Andreas; Kalinna, Bernd H.; Colman, Peter M.; Fairlie, W. Douglas

2011-01-01

Schistosomiasis is an infectious disease caused by parasites of the phylum platyhelminthe. Here, we describe the identification and characterization of a Bcl-2–regulated apoptosis pathway in Schistosoma japonicum and S. mansoni. Genomic, biochemical, and cell-based mechanistic studies provide evidence for a tripartite pathway, similar to that in humans including BH3-only proteins that are inhibited by prosurvival Bcl-2–like molecules, and Bax/Bak-like proteins that facilitate mitochondrial outer-membrane permeabilization. Because Bcl-2 proteins have been successfully targeted with “BH3 mimetic” drugs, particularly in the treatment of cancer, we investigated whether schistosome apoptosis pathways could provide targets for future antischistosomal drug discovery efforts. Accordingly, we showed that a schistosome prosurvival protein, sjA, binds ABT-737, a well-characterized BH3 mimetic. A crystal structure of sjA bound to a BH3 peptide provides direct evidence for the feasibility of developing BH3 mimetics to target Bcl-2 prosurvival proteins in schistosomes, suggesting an alternative application for this class of drugs beyond cancer treatment. PMID:21444803

Proteomic analysis of human skin treated with larval schistosome peptidases reveals distinct invasion strategies among species of blood flukes.

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Jessica Ingram

2011-09-01

Full Text Available Skin invasion is the initial step in infection of the human host by schistosome blood flukes. Schistosome larvae have the remarkable ability to overcome the physical and biochemical barriers present in skin in the absence of any mechanical trauma. While a serine peptidase with activity against insoluble elastin appears to be essential for this process in one species of schistosomes, Schistosoma mansoni, it is unknown whether other schistosome species use the same peptidase to facilitate entry into their hosts.Recent genome sequencing projects, together with a number of biochemical studies, identified alternative peptidases that Schistosoma japonicum or Trichobilharzia regenti could use to facilitate migration through skin. In this study, we used comparative proteomic analysis of human skin treated with purified cercarial elastase, the known invasive peptidase of S. mansoni, or S. mansoni cathespin B2, a close homolog of the putative invasive peptidase of S. japonicum, to identify substrates of either peptidase. Select skin proteins were then confirmed as substrates by in vitro digestion assays.This study demonstrates that an S. mansoni ortholog of the candidate invasive peptidase of S. japonicum and T. regenti, cathepsin B2, is capable of efficiently cleaving many of the same host skin substrates as the invasive serine peptidase of S. mansoni, cercarial elastase. At the same time, identification of unique substrates and the broader species specificity of cathepsin B2 suggest that the cercarial elastase gene family amplified as an adaptation of schistosomes to human hosts.

Iodine metabolism and thyroid functions in various species of domestic animals and poultry birds. II - Distribution of iodine-131 in developing ova in poultry birds

International Nuclear Information System (INIS)

Parshad, Omkar; Setia, M.S.; Rattan, P.J.S.; Sodhi, S.P.S.; Varman, P.N.

1974-01-01

To study the distribution of iodine in different stages of developing ova in relation to iodine metabolism, twentyfour healthy laying birds were randomly distributed into four groups of 6 birds each. Each bird was injected with 25.26 μCi. of carrier-free iodine-131. Afterwards, birds of group I, II, III and IV were sacrificed at 24, 48, 72 and 96 hours respectively. The results have revealed that : (i) the state of development of ovum may be an important factor in controlling the distribution of iodine in ova; (ii) the iodine may be found distributed in both the lipid as well as non-lipid fractions of the ova; (iii) most of the iodine in the ova may be present in the form of inorganic iodine whereas very minor amount of the iodine may be as butanol-extractable iodine and (iv) the changes in iodine content in different stages of development of ova observed during the present study may be considered to have a direct effect on the overall metabolism of iodine in the poultry birds. (author)

Exploring the function of protein kinases in schistosomes: perspectives from the laboratory and from comparative genomics

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Anthony John Walker

2014-07-01

Full Text Available Eukaryotic protein kinases are well conserved through evolution. The genome of Schistosoma mansoni, which causes intestinal schistosomiasis, encodes over 250 putative protein kinases with all of the main eukaryotic groups represented. However, unraveling functional roles for these kinases is a considerable endeavour, particularly as protein kinases regulate multiple and sometimes overlapping cell and tissue functions in organisms. In this article, elucidating protein kinase signal transduction and function in schistosomes is considered from the perspective of the state-of-the-art methodologies used and comparative organismal biology, with a focus on current advances and future directions. Using the free-living nematode Caenorhabditis elegans as a comparator we predict roles for various schistosome protein kinases in processes vital for host invasion and successful parasitism such as sensory behaviour, growth and development. It is anticipated that the characterization of schistosome protein kinases in the context of parasite function will catalyze cutting edge research into host-parasite interactions and will reveal new targets for developing drug interventions against human schistosomiasis.

Isolation and preservation of schistosome eggs and larvae in RNAlater® facilitates genetic profiling of individuals

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Webster Bonnie L

2009-10-01

Full Text Available Abstract Although field-sampling procedures to capture gDNA from individual schistosome larval stages directly from their natural hosts exist, they do pose some technical and logistical challenges hampering certain epidemiological studies. The aim of this study was to develop, refine and evaluate an alternative methodology, which enables better preservation of large numbers of individual schistosome larval stages and eggs collected in low resource endemic areas, to provide PCR-quality DNA for multi-locus genetic analysis. The techniques reported here present simple and effective short-term field and long-term laboratory preservation and storage systems for individually sampled schistosome eggs and larval stages using a commercially available aqueous stabilisation reagent, RNAlater® eliminating the need for more cumbersome resources such as refrigerators, heaters and centrifuge equipment for immediate specimen processing. Adaptations to a general gDNA extraction method are described, that enables the acquisition of a gDNA extract (~50 μl, facilitating multiple molecular analyses of each sampled schistosome. The methodology provided PCR-quality mitochondrial and nuclear DNA from laboratory cercariae, miracidia and eggs that had been stored at up to 37°C for 2 weeks and at 4°C for 6 months and also from field collected samples. This present protocol provides significant epidemiological, ethical and practical advantages over existing sampling methods and has the potential to be transferred to studies on other organisms, especially where specimens are unable to be seen by the naked eye, are difficult to handle and need to be obtained from a field environment.

S. haematobium as a common cause of genital morbidity in girls: a cross-sectional study of children in South Africa.

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Ingrid Elise Amlie Hegertun

Full Text Available BACKGROUND: Schistosoma (S. haematobium infection is a common cause of genital morbidity in adult women. Ova in the genital mucosal lining may cause lesions, bleeding, pain, discharge, and the damaged surfaces may pose a risk for HIV. In a heterogeneous schistosomiasis endemic area in South Africa, we sought to investigate if young girls had genital symptoms and if this was associated with urinary S. haematobium. METHODOLOGY: In a cross-sectional study of 18 randomly chosen primary schools, we included 1057 schoolgirls between the age of 10 and 12 years. We interviewed assenting girls, whose parents had consented to their participation and examined three urines from each of them for schistosome ova. PRINCIPAL FINDINGS: One third of the girls reported to have a history of genital symptoms. Prior schistosomal infection was reported by 22% (226/1020, this was associated with current genital symptoms (p<0.001. In regression analysis the genital symptoms were significantly associated both with urinary schistosomiasis (p<0.001 and water contact (p<0.001. CONCLUSIONS: Even before sexually active age, a relatively large proportion of the participating girls had similar genital symptoms to those reported for adult genital schistosomiasis previously. Anti-schistosomal treatment should be considered at a young age in order to prevent chronic genital damage and secondary infections such as HIV, sexually transmitted diseases and other super-infections.

Prevalence of Strongyle ova in Goats and comparative studies of ...

African Journals Online (AJOL)

ADOWIE PERE

2018-01-16

Jan 16, 2018 ... Keywords: Goats, Strongyle ova, Faecal Culture Techniques, Prevalence,. The Nigerian goat ... km located in the North eastern corner of Nigeria ... teaching and research farm, Maiduguri metropolitan ... West African Dwarf. 5.

Detection of parasite ova and egg in commonly consumed ...

African Journals Online (AJOL)

Vegetables are important sources of nutrients, however infections arising from consumption of contaminated vegetables continue to cause serious public health problems leading to thousands of death cases yearly. This study was conducted to detect parasite ova and egg in commonly consumed vegetables in Makurdi, ...

Splenic artery ligature associated with endoscopic banding for schistosomal portal hypertension.

Science.gov (United States)

Colaneri, Renata Potonyacz; Coelho, Fabrício Ferreira; de Cleva, Roberto; Perini, Marcos Vinícius; Herman, Paulo

2014-11-28

To propose a less invasive surgical treatment for schistosomal portal hypertension. Ten consecutive patients with hepatosplenic schistosomiasis and portal hypertension with a history of upper gastrointestinal hemorrhage from esophageal varices rupture were evaluated in this study. Patients were subjected to a small supraumbilical laparotomy with the ligature of the splenic artery and left gastric vein. During the procedure, direct portal vein pressure before and after the ligatures was measured. Upper gastrointestinal endoscopy was performed at the 30(th) postoperative day, when esophageal varices diameter were measured and band ligature performed. During follow-up, other endoscopic procedures were performed according to endoscopy findings. There was no intra-operative mortality and all patients had confirmed histologic diagnoses of schistosomal portal hypertension. During the immediate postoperative period, two of the ten patients had complications, one characterized by a splenic infarction, and the other by an incision hematoma. Mean hospitalization time was 4.1 d (range: 2-7 d). Pre- and post-operative liver function tests did not show any significant changes. During endoscopy thirty days after surgery, a decrease in variceal diameters was observed in seven patients. During the follow-up period (57-72 mo), endoscopic therapy was performed and seven patients had their varices eradicated. Considering the late postoperative evaluation, nine patients had a decrease in variceal diameters. A mean of 3.9 endoscopic banding sessions were performed per patient. Two patients presented bleeding recurrence at the late postoperative period, which was controlled with endoscopic banding in one patient due to variceal rupture and presented as secondary to congestive gastropathy in the other patient. Both bleeding episodes were of minor degree with no hemodynamic consequences or need for blood transfusion. Ligature of the splenic artery and left gastric vein with supraumbilical

Impact of schistosome infection on Plasmodium falciparum Malariometric indices and immune correlates in school age children in Burma Valley, Zimbabwe.

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Davison T Sangweme

2010-11-01

Full Text Available A group of children aged 6-17 years was recruited and followed up for 12 months to study the impact of schistosome infection on malaria parasite prevalence, density, distribution and anemia. Levels of cytokines, malaria specific antibodies in plasma and parasite growth inhibition capacities were assessed. Baseline results suggested an increased prevalence of malaria parasites in children co-infected with schistosomiasis (31% compared to children infected with malaria only (25% (p = 0.064. Moreover, children co-infected with schistosomes and malaria had higher sexual stage geometric mean malaria parasite density (189 gametocytes/µl than children infected with malaria only (73/µl gametocytes (p = 0.043. In addition, a larger percentage of co-infected children (57% had gametocytes as observed by microscopy compared to the malaria only infected children (36% (p = 0.06. There was no difference between the two groups in terms of the prevalence of anemia, which was approximately 64% in both groups (p = 0.9. Plasma from malaria-infected children exhibited higher malaria antibody activity compared to the controls (p = 0.001 but was not different between malaria and schistosome plus malaria infected groups (p = 0.44 and malaria parasite growth inhibition activity at baseline was higher in the malaria-only infected group of children than in the co-infected group though not reaching statistical significance (p = 0.5. Higher prevalence and higher mean gametocyte density in the peripheral blood may have implications in malaria transmission dynamics during co-infection with helminths.

Synthesis and evaluation of 1,4-naphthoquinone ether derivatives as SmTGR inhibitors and new anti-schistosomal drugs.

Science.gov (United States)

Johann, Laure; Belorgey, Didier; Huang, Hsin-Hung; Day, Latasha; Chessé, Matthieu; Becker, Katja; Williams, David L; Davioud-Charvet, Elisabeth

2015-08-01

Investigations regarding the chemistry and mechanism of action of 2-methyl-1,4-naphthoquinone (or menadione) derivatives revealed 3-phenoxymethyl menadiones as a novel anti-schistosomal chemical series. These newly synthesized compounds (1-7) and their difluoromethylmenadione counterparts (8, 9) were found to be potent and specific inhibitors of Schistosoma mansoni thioredoxin-glutathione reductase (SmTGR), which has been identified as a potential target for anti-schistosomal drugs. The compounds were also tested in enzymic assays using both human flavoenzymes, i.e. glutathione reductase (hGR) and selenium-dependent human thioredoxin reductase (hTrxR), to evaluate the specificity of the inhibition. Structure-activity relationships as well as physico- and electro-chemical studies showed a high potential for the 3-phenoxymethyl menadiones to inhibit SmTGR selectively compared to hGR and hTrxR enzymes, in particular those bearing an α-fluorophenol methyl ether moiety, which improves anti-schistosomal action. Furthermore, the (substituted phenoxy)methyl menadione derivative (7) displayed time-dependent SmTGR inactivation, correlating with unproductive NADPH-dependent redox cycling of SmTGR, and potent anti-schistosomal action in worms cultured ex vivo. In contrast, the difluoromethylmenadione analog 9, which inactivates SmTGR through an irreversible non-consuming NADPH-dependent process, has little killing effect in worms cultured ex vivo. Despite ex vivo activity, none of the compounds tested was active in vivo, suggesting that the limited bioavailability may compromise compound activity. Therefore, future studies will be directed toward improving pharmacokinetic properties and bioavailability. © 2015 FEBS.

Enterobius vermicularis as a Novel Surrogate for the Presence of Helminth Ova in Tertiary Wastewater Treatment Plants.

Science.gov (United States)

Rudko, Sydney P; Ruecker, Norma J; Ashbolt, Nicholas J; Neumann, Norman F; Hanington, Patrick C

2017-06-01

Significant effort has gone into assessing the fate and removal of viruses, bacteria, and protozoan parasites during wastewater treatment to provide data addressing potential health risks associated with reuse options. Comparatively less is known about the fate of parasitic worm species ova in these complex systems. It is largely assumed that these helminths settle, are removed with the sludge, and consequently represent a relatively low risk for wastewater reuse applications. However, helminths are a highly diverse group of organisms that display a wide range of physical properties that complicate the application of a single treatment for helminth reduction during wastewater treatment. Moreover, their diverse biological and physical properties make some ova highly resistant to both disinfection (i.e., with chlorine or UV treatment) and physical removal (settling) through the wastewater treatment train, indicating that there may be reason to broaden the scope of our investigations into whether parasitic worm eggs can be identified in treated wastewater. The ubiquitous human parasitic nematode Enterobius vermicularis (pinworm) produces small, buoyant ova. Utilizing a novel diagnostic quantitative PCR (qPCR), this study monitored E. vermicularis presence at two full-scale wastewater treatment plants over the course of 8 months and demonstrated incomplete physical removal of E. vermicularis ova through tertiary treatment, with removal efficiencies approximating only 0.5 and 1.6 log 10 at the two wastewater treatment plants based on qPCR. These findings demonstrate the need for more-diverse surrogates of helminthic ova to fully assess treatment performance with respect to reclaimed wastewaters. IMPORTANCE Helminths, despite being a diverse and environmentally resistant class of pathogens, are often underestimated and ignored when treatment performance at modern wastewater treatment plants is considered. A one-size-fits-all surrogate for removal of helminth ova may be

An ultrastructural study of ova of Paragonimus species from human ...

African Journals Online (AJOL)

Ova of Paragonimus species were observed in faecal specimens from a paediatric patient at King Edward VIII Hospital and from a cat from the Durban area. The material was embedded in low-viscosity epoxy resin and examined under the electron microscope. Although P. kellicotti has been found in the cat in South Africa, ...

Acute toxemic schistosomiasis complicated by a acute flaccid paraplegia due to schistosomal myeloradiculopathy in Sudan

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Ahmed, Abdelmonim F [Dept. of Medicine, Faculty of Medicine, Taibah Univ., Al-Madinah Al-Munwarah (Saudi Arabia); Kareem, Abid M [Dept. of Gastroenterology, King Fahd Hospital, Al- Madinah Al-Munwarah (Saudi Arabia); Dawoud, Talal A [Dept. of Neurology, King Fahd Hospital, Al-Madinah Al-Munawarh (Saudi Arabia); Idris, Abdelrehman S [Dept. of Neurology, Hiraa Hospital, Mecca (Saudi Arabia)

2008-07-01

A 55-year old Sudanese physician presented with one month history of diarrhea, loss of weight 10 kg and low grade nocturnal fever. Following colonoscopy, he rapidly developed paraparesis and retention of urine. Magnetic resonance imaging (MRI) of the spinal cord showed low cord lesion suggestive of transverse myelitis. We present a detailed account of diagnostic and management challenges and a literature review of the final diagnosis of acute toxemic schistosomiasis, complicated by acute flaccid paraplegia due to schistosomal myeloradiculopathy. We are reporting this case to increase the awareness of physicians of schistosomal myeloradiculopathy, as it needs urgent specific treatment praziquantel and steroids. An early follow-up with MRI of the spinal cord 2 weeks treatment may help in preventing unnecessary neurosurgical intervention. Bilharziasis may be contracted on the banks of river White Nile in urban areas. Finally clinicians should make use of the Google search for diagnosis in difficult cases. (author)

Acute toxemic schistosomiasis complicated by a acute flaccid paraplegia due to schistosomal myeloradiculopathy in Sudan

International Nuclear Information System (INIS)

Ahmed, Abdelmonim F.; Kareem, Abid M.; Dawoud, Talal A.; Idris, Abdelrehman S.

2008-01-01

A 55-year old Sudanese physician presented with one month history of diarrhea, loss of weight 10 kg and low grade nocturnal fever. Following colonoscopy, he rapidly developed paraparesis and retention of urine. Magnetic resonance imaging (MRI) of the spinal cord showed low cord lesion suggestive of transverse myelitis. We present a detailed account of diagnostic and management challenges and a literature review of the final diagnosis of acute toxemic schistosomiasis, complicated by acute flaccid paraplegia due to schistosomal myeloradiculopathy. We are reporting this case to increase the awareness of physicians of schistosomal myeloradiculopathy, as it needs urgent specific treatment praziquantel and steroids. An early follow-up with MRI of the spinal cord 2 weeks treatment may help in preventing unnecessary neurosurgical intervention. Bilharziasis may be contracted on the banks of river White Nile in urban areas. Finally clinicians should make use of the Google search for diagnosis in difficult cases. (author)

Effect of oral administration of Propionibacterium acnes on growth performance, DTH response and anti-OVA titers in goat kids

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Luis Miguel Ferrer

2013-01-01

Full Text Available Immunostimulants are susbstances that stimuli the response of effector cells to activate the immune response such as antigen uptake, cytokine release or antibody response. These substances can increase resistence to infection by different types of microorganisms, reducing dependence of antibiotics used in livestock animals. Recent reports have demonstrated the positive effect of Propionibacterium acnes (P. acnes to control animal diseases. In this study, we evaluated the effect of the non-specific immunostimulant P. acnes on immunological functions and growth performance in goat kids. Twenty five goat kids served as control group (A and another 25 animals received P. acnes being the experimental group (B. Kids were challenged with ovalbumin (OVA to assess humoral immunity. To assess in vivo cell immunity, delayed type hypersensitivity (DTH test with phytohemagglutinin (PHA was used, clinical signs and body weight were recorded each week until 9 weeks of age when the experiment ended. Blood samples were obtained to analyze serum proteins fractions and anti-OVA specific antibodies. No clinical signs of disease and no differences (p>0.05 on body weight between groups were recorded (7.32±0.81 kg in group A, 7.13±0.65 kg in group B. Goat kids from group B had more total protein (59.8±5g/l and albumin levels (32.8±3.3g/l than goat kids from group A (56.6±5.7 g/l, 29.6±3.9 g/l respectively (p<0.05. DTH response in goat kids from group B on day 42 was higher (p<0.05 than group A. At day 63, goat kids from group receiving P. acnes had higher percentage (85.4 of anti-OVA IgM titers (p<0.05 than control group (57.7. In conclusion, the results showed that oral administration of P. acnes to goat kids improved some aspects of the immune system of the animals and it could be used to control goat diseases.

The Ontology of Vaccine Adverse Events (OVAE) and its usage in representing and analyzing adverse events associated with US-licensed human vaccines.

Science.gov (United States)

Marcos, Erica; Zhao, Bin; He, Yongqun

2013-11-26

Licensed human vaccines can induce various adverse events (AE) in vaccinated patients. Due to the involvement of the whole immune system and complex immunological reactions after vaccination, it is difficult to identify the relations among vaccines, adverse events, and human populations in different age groups. Many known vaccine adverse events (VAEs) have been recorded in the package inserts of US-licensed commercial vaccine products. To better represent and analyze VAEs, we developed the Ontology of Vaccine Adverse Events (OVAE) as an extension of the Ontology of Adverse Events (OAE) and the Vaccine Ontology (VO). Like OAE and VO, OVAE is aligned with the Basic Formal Ontology (BFO). The commercial vaccines and adverse events in OVAE are imported from VO and OAE, respectively. A new population term 'human vaccinee population' is generated and used to define VAE occurrence. An OVAE design pattern is developed to link vaccine, adverse event, vaccinee population, age range, and VAE occurrence. OVAE has been used to represent and classify the adverse events recorded in package insert documents of commercial vaccines licensed by the USA Food and Drug Administration (FDA). OVAE currently includes over 1,300 terms, including 87 distinct types of VAEs associated with 63 human vaccines licensed in the USA. For each vaccine, occurrence rates for every VAE in different age groups have been logically represented in OVAE. SPARQL scripts were developed to query and analyze the OVAE knowledge base data. To demonstrate the usage of OVAE, the top 10 vaccines accompanying with the highest numbers of VAEs and the top 10 VAEs most frequently observed among vaccines were identified and analyzed. Asserted and inferred ontology hierarchies classify VAEs in different levels of AE groups. Different VAE occurrences in different age groups were also analyzed. The ontology-based data representation and integration using the FDA-approved information from the vaccine package insert documents

Molecular phylogenetics of the elephant schistosome Bivitellobilharzia loxodontae (Trematoda: Schistosomatidae) from the Central African Republic

Czech Academy of Sciences Publication Activity Database

Brant, S. V.; Pomajbíková, K.; Modrý, David; Petrželková, Klára Judita; Todd, A.; Loker, E. S.

2013-01-01

Roč. 87, č. 01 (2013), s. 102-107 ISSN 0022-149X R&D Projects: GA ČR GA206/09/0927 Institutional research plan: CEZ:AV0Z60220518 Institutional support: RVO:68081766 ; RVO:60077344 Keywords : schistosomes * elephant Subject RIV: EG - Zoology Impact factor: 1.303, year: 2013

[Demand for and the Development of Detection Techniques for Source of Schistosome Infection in China].

Science.gov (United States)

Wang, Shi-ping; He, Xin; Zhou, Yun-fei

2015-12-01

Schistosomiasis is a type of zoonotic parasitosis that severely impairs human health. Rapid detection of infection sources is a key to the control of schistosomiasis. With the effective control of schistosomiasis in China, the detection techniques for infection sources have also been developed. The rate and the intensity of infection among humans and livestocks have been significantly decreased in China, as the control program has entered the transmission control stage in most of the endemic areas. Under this situation, the traditional etiological diagnosing techniques and common immunological methods can not afford rapid detection of infection sources of schistosomiasis. Instead, we are calling for detection methods with higher sensitivity, specificity and stability while being less time-consuming, more convenient and less costing. In recent years, many improved or novel detection methods have been applied for the epidemiological surveillance of schistosomiasis, such as the automatic scanning microscopic image acquisition system, PCR-ELISA, immunosensors, loop-mediated isothermal amplification, etc. The development of new monitoring techniques can facilitate rapid detection of schistosome infection sources in endemic areas.

Development of a Schistosoma mansoni shotgun O-glycan microarray and application to the discovery of new antigenic schistosome glycan motifs.

Science.gov (United States)

van Diepen, Angela; van der Plas, Arend-Jan; Kozak, Radoslaw P; Royle, Louise; Dunne, David W; Hokke, Cornelis H

2015-06-01

Upon infection with Schistosoma, antibody responses are mounted that are largely directed against glycans. Over the last few years significant progress has been made in characterising the antigenic properties of N-glycans of Schistosoma mansoni. Despite also being abundantly expressed by schistosomes, much less is understood about O-glycans and antibody responses to these have not yet been systematically analysed. Antibody binding to schistosome glycans can be analysed efficiently and quantitatively using glycan microarrays, but O-glycan array construction and exploration is lagging behind because no universal O-glycanase is available, and release of O-glycans has been dependent on chemical methods. Recently, a modified hydrazinolysis method has been developed that allows the release of O-glycans with free reducing termini and limited degradation, and we applied this method to obtain O-glycans from different S. mansoni life stages. Two-dimensional HPLC separation of 2-aminobenzoic acid-labelled O-glycans generated 362 O-glycan-containing fractions that were printed on an epoxide-modified glass slide, thereby generating the first shotgun O-glycan microarray containing naturally occurring schistosome O-glycans. Monoclonal antibodies and mass spectrometry showed that the O-glycan microarray contains well-known antigenic glycan motifs as well as numerous other, potentially novel, antibody targets. Incubations of the microarrays with sera from Schistosoma-infected humans showed substantial antibody responses to O-glycans in addition to those observed to the previously investigated N- and glycosphingolipid glycans. This underlines the importance of the inclusion of these often schistosome-specific O-glycans in glycan antigen studies and indicates that O-glycans contain novel antigenic motifs that have potential for use in diagnostic methods and studies aiming at the discovery of vaccine targets. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights

IMPROVEMENT OF SCHISTOSOMAL PORTAL HYPERTENSIVE COLOPATHY AFTER SURGICAL TREATMENT

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Maria Angelina Carvalho MIRANDA

2013-04-01

Full Text Available Context Data on vascular alterations in patients with hepatosplenic schistosomiasis and portal hypertensive colopathy and changes in these after surgery to decrease portal hypertension are limited. Objective The purpose of this study was to analyse the alterations of portal hypertensive colopathy previously and 6-12 months after splenectomy and gastric devascularization. Methods Twelve patients with hepatosplenic schistosomiasis who also had upper gastrointestinal bleeding were studied prospectively. Their endoscopic findings before and 6-12 months after the surgery were analysed. In addition, mucosal biopsies from ascending colon, sigmoid colon and rectum at these time points were subjected to histological and histomorphometric assessment. It was used a control group due to lack of normal pattern of the histomorphometric measures of vessels in individuals without portal hypertension. The critical level of significance adopted in all tests was of a maximum probability error of 5%. Results Surgery did not lead to significant improvement in histological and endoscopic findings. However, on histomorphometry, there was a significant decrease in the area, diameter and thickness of the vessels in mucosa at all colonic sites. Conclusion Surgery for decompression of schistosomal portal hypertension has a beneficial effect on the associated colopathy, being best indicated in patients with gastrointestinal bleeding and esophageal varices.

Hyperplasia of elastic tissue in hepatic schistosomal fibrosis

Directory of Open Access Journals (Sweden)

Zilton A. Andrade

1991-12-01

Full Text Available Elastic tissue hyperplasia, revealed by means of histological, immunocytochemical and ultrastructural methods, appeared as a prominent change in surgical liver biopsies taken from 61 patients with schistosomal periportal and septal fibrosis. Such hyperplasia was absent in ecperimental murine schistosomiasis, including mice with "pipe-stem" fibrosis. Displaced connective tissue cells in periportal areas, such as smooth muscle cells, more frequently observed in human material, could be the site of excessive elastin synthesis, and could explain the differences observed in human and experimental materials. Elastic tissue, sometimes represented by its microfibrillar components, also appeared to be more condensed in areas of matrix (collagen degradation, suggesting a participation of this tissue in the remodelling of the extracellular matrix. By its rectratile properties elastic tissue hyperplasia in hepatic schistosomiasis can cause vascular narrowing and thus play a role in the pathogenesis of portal hypeertension.

CONTROL OF SCHISTOSOMIASIS IN THE GEZIRA IRRIGATION SCHEME, SUDAN.

Science.gov (United States)

Amin, Mutamad; Abubaker, Hwiada

2017-01-01

This paper analyses the changing patterns of infection with Schistosoma mansoni and S. haematobium in the Gezira Irrigation Scheme, Sudan. Taking a historical perspective, it shows the way in which factors such as ecology, biology, social and economic variables and politics have shaped patterns of infection, and how different kinds of strategies have been developed to control schistosomal infection over time. Wider political and economic issues at both national and international levels have shaped these strategies, influencing the prevalence and intensity of schistosomal infection at a local level. By highlighting the inter-play between the above-mentioned factors, the article reflects on the wisdom of prioritizing community-directed mass drug administration for the control of schistosomiasis in Gezira and elsewhere. The review demonstrates that not all efforts to control schistosomiasis are sustainable. A comprehensive control strategy involving political commitment, community participation and socioeconomic development is important for sustainable control of schistosomal infection.

Ova collection in Japan: making visible women’s experience in male spaces

NARCIS (Netherlands)

Kato, M.; Sleeboom-Faulkner, M.

2013-01-01

The role of women is essential in embryo creation and donation, as they undergo in vitro fertilisation (IVF) treatment for ova collection. Yet, it has often been pointed out that in the process of embryo donation women's role is largely neglected, as if embryos come from nowhere. The procedure of

Genetic dissimilarity between mates, but not male heterozygosity, influences divorce in schistosomes.

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Sophie Beltran

Full Text Available BACKGROUND: Correlational studies strongly suggest that both genetic similarity and heterozygosity can influence female mate choice. However, the influence of each variable has usually been tested independently, although similarity and heterozygosity might be correlated. We experimentally determined the relative influence of genetic similarity and heterozygosity in divorce and re-mating in the monogamous endoparasite Schistosoma mansoni. METHODOLOGY/PRINCIPAL FINDINGS: We performed sequential infections of vertebrate hosts with controlled larval populations of parasites, where sex and individual genetic diversity and similarity were predetermined before infection. Divorce rate increased significantly when females were given the opportunity to increase genetic dissimilarity through re-mating with a new partner, independently of the intensity of male-male competition. We found however no evidence for females attempting to maximize the level of heterozygosity of their reproductive partner through divorce. CONCLUSIONS/SIGNIFICANCE: Female preference for genetically dissimilar males should result in more heterozygous offspring. Because genetic heterozygosity might partly determine the ability of parasites to counter host resistance, adaptive divorce could be an important factor in the evolutionary arms race between schistosomes and their hosts.

Immunization of cattle against Schistosome bovis (including pathophysiological studies on schistosome infection in bovines)

International Nuclear Information System (INIS)

Hussain, M.F.

1978-12-01

Bovine schistosomiasis caused by S. bovis constitutes a serious veterinary problem in the Sudan, yet very little is known about the epidemiology, pathogenesis and immunology of the disease. Over the past 5 years, work on these aspects has been conducted at Khartoum and several outlying areas of the White Nile Province in Sudan. In studies involving over 1,000 cattle, it was found that almost 100% of animals are infected by 2 years of age but that the prevalence falls to less than 60% over the following 7 years. There was also a marked reduction in the intensity of infection with increasing age, indicating the development of a high degree of acquired resistance. This was confirmed experimentally by challenging animals from an endemic area with massive numbers of cercariae. These animals completely resisted the challenge whereas animals never previously exposed either died or became moribund due to the severe haemorrhagic diarrhoea resulting from the passage of schistosome eggs through the gut wall. Attempts were made to vaccinate calves using irradiated organisms. These gave 70-80% protection against a challenge infection and this was sufficient to allow these animals to gain weight and remain clinically healthy. Animals not given the vaccine deteriorated. The efficacy of the vaccine was then tested under field conditions and found to give a high level of protection against S. bovis. These animals were also less susceptible to intercurrent infections

Preventive Intra Oral Treatment of Sea Cucumber Ameliorate OVA-Induced Allergic Airway Inflammation.

Science.gov (United States)

Lee, Da-In; Park, Mi-Kyung; Kang, Shin Ae; Choi, Jun-Ho; Kang, Seok-Jung; Lee, Jeong-Yeol; Yu, Hak Sun

2016-01-01

Sea cucumber extracts have potent biological effects, including anti-viral, anti-cancer, antibacterial, anti-oxidant, and anti-inflammation effects. To understand their anti-asthma effects, we induced allergic airway inflammation in mice after 7 oral administrations of the extract. The hyper-responsiveness value in mice with ovalbumin (OVA)-alum-induced asthma after oral injection of sea cucumber extracts was significantly lower than that in the OVA-alum-induced asthma group. In addition, the number of eosinophils in the lungs of asthma-induced mice pre-treated with sea cucumber extract was significantly decreased compared to that of PBS pre-treated mice. Additionally, CD4[Formula: see text]CD25[Formula: see text]Foxp3[Formula: see text]T (regulatory T; Treg) cells significantly increased in mesenteric lymph nodes after 7 administrations of the extract. These results suggest that sea cucumber extract can ameliorate allergic airway inflammation via Treg cell activation and recruitment to the lung.

In ova angiogenesis analgesic and anti inflammatory potency of Aerva monsoniae (Amaranthaceae

Directory of Open Access Journals (Sweden)

Sandhya S

2012-10-01

Full Text Available Objective: To evaluate the wound healing potency of aqueous extract of Aerva monsoniae (A. monsoniae by in vitro method using fertilized eggs, in vivo analgesic and anti inflammatory activity in rodents and the anti bacterial activity on the bacterial strains that infect the wound. Methods: The whole plant of A. monsoniae was extracted with water and then subjected to preliminary chemical screening. It was then evaluated for in ova angiogenesis on fertilized white leg horn eggs using the concentrations of 200-600 毺 g/mL. The analgesic activity was evaluated in mice using the dose 100 and 250 mg/kg. The anti inflammatory activity was evaluated in rats using the dose 250 mg/kg and 500 mg/kg. In both the parameters water was used as the control and diclofenac was used the standard. The anti bacterial activity on Staphylococcus aureus and Pseudomonas aerugenosa was performed. Results: The phytochemical screening revealed the presence of tannins, flavonoids and saponins. The in ova angiogenesis revealed a dose dependent activity which proves the wound healing claim of the plant as more number of blood capillaries were formed at the site of the drug. The plant proved to be a potent analgesic and anti inflammatory agent at doses 1 00 mg/kg and 250 mg/kg. The anti bacterial activity was present but at higher doses. Conclusions: The parameters studied in the present investigation proved that the plant is a potent wound healer. Further in vivo wound healing studies on animal model is desired. As the extract showed potent analgesic, anti inflammatory and anti bacterial properties, it can be considered that when formulated into suitable formulation, and it can reduce the pain, inflammation and infections related to wound very well.

Schistosome tegumental ecto-apyrase (SmATPDase1 degrades exogenous pro-inflammatory and pro-thrombotic nucleotides

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Akram A. Da’dara

2014-03-01

Full Text Available Schistosomes are parasitic worms that can survive in the hostile environment of the human bloodstream where they appear refractory to both immune elimination and thrombus formation. We hypothesize that parasite migration in the bloodstream can stress the vascular endothelium causing this tissue to release chemicals alerting responsive host cells to the stress. Such chemicals are called damage associated molecular patterns (DAMPs and among the most potent is the proinflammatory mediator, adenosine triphosphate (ATP. Furthermore, the ATP derivative ADP is a pro-thrombotic molecule that acts as a strong activator of platelets. Schistosomes are reported to possess at their host interactive tegumental surface a series of enzymes that could, like their homologs in mammals, degrade extracellular ATP and ADP. These are alkaline phosphatase (SmAP, phosphodiesterase (SmNPP-5 and ATP diphosphohydrolase (SmATPDase1. In this work we employ RNAi to knock down expression of the genes encoding these enzymes in the intravascular life stages of the parasite. We then compare the abilities of these parasites to degrade exogenously added ATP and ADP. We find that only SmATPDase1-suppressed parasites are significantly impaired in their ability to degrade these nucleotides. Suppression of SmAP or SmNPP-5 does not appreciably affect the worms’ ability to catabolize ATP or ADP. These findings are confirmed by the functional characterization of the enzymatically active, full-length recombinant SmATPDase1 expressed in CHO-S cells. The enzyme is a true apyrase; SmATPDase1 degrades ATP and ADP in a cation dependent manner. Optimal activity is seen at alkaline pH. The Km of SmATPDase1 for ATP is 0.4 ± 0.02 mM and for ADP, 0.252 ± 0.02 mM. The results confirm the role of tegumental SmATPDase1 in the degradation of the exogenous pro-inflammatory and pro-thrombotic nucleotides ATP and ADP by live intravascular stages of the parasite. By degrading host inflammatory signals

HPLC-ESI-MS Characterization of Certain Polyphenolic Compounds of Carica papaya L. Fruit Extracts and Evaluation of Their Potential Against Murine Schistosomiasis mansoni.

Science.gov (United States)

Abdel-Lateef, Ezzat El-Sayed; Rabia, Ibrahim Aly; El-Sayed, Mortada Mohamed; Abdel-Hameed, El-Sayed Saleh

2018-04-10

The in vivo antischistosomal activities of Carica papaya L. extracts were evaluated and the characterization of the active secondary metabolites of the defatted methanolic extract was performed using HPLC-ESI-MS. The plant fruit powders were extracted with 85% methanol and fractionated using organic solvents. The in vivo antischistosomal effects of the methanolic extracts and its fractions, as well as the assessment of the relationship between the antischistosomal activity of these plant extracts and oxidative stress, was determined. In addition, the defatted methanolic extract was characterized by HPLC-ESI-MS analysis. The number of worms, ova, and the Oogram pattern displayed typical Schistosoma mansoni pathology 8 weeks after infection in mice. Treatment of the infected group with the defatted methanolic extracts significantly decreased worm burden, immature ova and mature ova, while increasing the percentage of dead ova in vivo. The butanol fraction was the most effective fraction reducing worm burden by 77%, ova count in the intestine by 76% and in the liver by 80%, and significantly decreased immature and mature ova ( P group. Additionally, the defatted methanolic extracts improved the reduced glutathione and malondialdehyde levels in hepatic tissues in the treated groups compared to the infected group. The HPLC-ESI-MS analysis of the Carica papaya defatted methanolic extract revealed the presence of several polyphenolic compounds. Carica papaya fruit extracts are rich with phenolic acids and flavonoids and show a significant effect against S. mansoni infections which may be used alternative to PZQ as anti-schistosomal drug against schistosomiasis. © Georg Thieme Verlag KG Stuttgart · New York.

Schistosome circulating anodic antigen in serum of individuals infected with Schistosoma japonicum from the Philippines before and after chemotherapy with praziquantel

NARCIS (Netherlands)

van 't Wout, A. B.; de Jonge, N.; Tiu, W. U.; Garcia, E. E.; Mitchell, G. F.; Deelder, A. M.

1992-01-01

The presence of the schistosome circulating anodic antigen (CAA) in serum of patients infected with Schistosoma japonicum from The Philippines has been investigated using an enzyme-linked immunosorbent assay (ELISA). Serum samples were tested from 48 patients who excreted S. japonicum eggs, 9

A Case of Squamous Cell Carcinoma of the Renal Pelvis in association with Schistosoma hematobium

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Muhammad A. A. Khan

2012-01-01

Full Text Available A 72-year-old man presented with painless frank haematuria. Investigations included intravenous urogram and abdominal/pelvic CT which revealed a marked focal thickening of the wall of the inferior aspect of the left renal pelvis extending into the lower pole calyx and into the pelviureteric junction resulting in left hydronephrosis. Urine cytology demonstrated clusters of malignant keratinised squamous cells and schistosome ova. He underwent left laparoscopic radical nephroureterectomy and histology revealed moderately differentiated keratinising squamous cell carcinoma in the renal pelvis.

Regulation of schistosome egg production by HMG CoA reductase

International Nuclear Information System (INIS)

VandeWaa, E.A.; Bennett, J.L.

1986-01-01

Hydroxymethylglutaryl coenzyme A reductase (HMG CoA reductase) catalyzes the conversion of HMG CoA to mevalonate in the synthesis of steroids, isoprenoids and terpenes. Mevinolin, an inhibitor of this enzyme, decreased egg production in Schistosoma mansoni during in vitro incubations. This was associated with a reduction in the incorporation of 14 C-acetate into polyisoprenoids and a reduction in the formation of a lipid-linked oligosaccharide. In vivo, mevinolin in daily doses of 50 mg/kg (p.o., from days 30-48 post-infection) caused no change in gross liver pathology in S. mansoni infected mice. However, when parasites exposed to mevinolin or its vehicle in vivo were cultured in vitro, worms from mevinolin-treated mice produced six times more eggs than control parasites. When infected mice were dosed with 250 mg/kg mevinolin daily (p.o., from days 35-45 post-infection), liver pathology was reduced in comparison to control mice. Thus, during in vivo exposure to a high dose of the drug egg production is decreased, while at a lower dose it appears unaffected until the parasites are cultured in a drug-free in vitro system wherein egg production is stimulated to extraordinarily high levels. It may be that at low doses mevinolin, by inhibiting the enzyme, is blocking the formation of a product (such as an isoprenoid) which normally acts to down-regulate enzyme synthesis, resulting in enzyme induction. Induction of HMG CoA reductase is then expressed as increased egg production when the worms are removed from the drug. These data suggest that HMG CoA reductase plays a role in schistosome egg production

Podnikatelský plán restaurace Kovářova kobyla

OpenAIRE

Lainková, Jana

2017-01-01

The objectiv of the thesis is to create a business plan for a Kovářova kobyla restaurant. The business plan is for first year, which is complete and that is 2017. The plan helps find out if restaurant is cost-effective. At first there will be theoretically explained business plan with all parts. The next step is description legislation for business and legislation for food industry. This thesis continues with processing of business plan including financial plan and financial analysis. At the ...

Application of RNAi to Genomic Drug Target Validation in Schistosomes.

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Alessandra Guidi

2015-05-01

Full Text Available Concerns over the possibility of resistance developing to praziquantel (PZQ, has stimulated efforts to develop new drugs for schistosomiasis. In addition to the development of improved whole organism screens, the success of RNA interference (RNAi in schistosomes offers great promise for the identification of potential drug targets to initiate drug discovery. In this study we set out to contribute to RNAi based validation of putative drug targets. Initially a list of 24 target candidates was compiled based on the identification of putative essential genes in schistosomes orthologous of C. elegans essential genes. Knockdown of Calmodulin (Smp_026560.2 (Sm-Calm, that topped this list, produced a phenotype characterised by waves of contraction in adult worms but no phenotype in schistosomula. Knockdown of the atypical Protein Kinase C (Smp_096310 (Sm-aPKC resulted in loss of viability in both schistosomula and adults and led us to focus our attention on other kinase genes that were identified in the above list and through whole organism screening of known kinase inhibitor sets followed by chemogenomic evaluation. RNAi knockdown of these kinase genes failed to affect adult worm viability but, like Sm-aPKC, knockdown of Polo-like kinase 1, Sm-PLK1 (Smp_009600 and p38-MAPK, Sm-MAPK p38 (Smp_133020 resulted in an increased mortality of schistosomula after 2-3 weeks, an effect more marked in the presence of human red blood cells (hRBC. For Sm-PLK-1 the same effects were seen with the specific inhibitor, BI2536, which also affected viable egg production in adult worms. For Sm-PLK-1 and Sm-aPKC the in vitro effects were reflected in lower recoveries in vivo. We conclude that the use of RNAi combined with culture with hRBC is a reliable method for evaluating genes important for larval development. However, in view of the slow manifestation of the effects of Sm-aPKC knockdown in adults and the lack of effects of Sm-PLK-1 and Sm-MAPK p38 on adult viability

Mobile Diagnostics Based on Motion? A Close Look at Motility Patterns in the Schistosome Life Cycle

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Ewert Linder

2016-06-01

Full Text Available Imaging at high resolution and subsequent image analysis with modified mobile phones have the potential to solve problems related to microscopy-based diagnostics of parasitic infections in many endemic regions. Diagnostics using the computing power of “smartphones” is not restricted by limited expertise or limitations set by visual perception of a microscopist. Thus diagnostics currently almost exclusively dependent on recognition of morphological features of pathogenic organisms could be based on additional properties, such as motility characteristics recognizable by computer vision. Of special interest are infectious larval stages and “micro swimmers” of e.g., the schistosome life cycle, which infect the intermediate and definitive hosts, respectively. The ciliated miracidium, emerges from the excreted egg upon its contact with water. This means that for diagnostics, recognition of a swimming miracidium is equivalent to recognition of an egg. The motility pattern of miracidia could be defined by computer vision and used as a diagnostic criterion. To develop motility pattern-based diagnostics of schistosomiasis using simple imaging devices, we analyzed Paramecium as a model for the schistosome miracidium. As a model for invasive nematodes, such as strongyloids and filaria, we examined a different type of motility in the apathogenic nematode Turbatrix, the “vinegar eel.” The results of motion time and frequency analysis suggest that target motility may be expressed as specific spectrograms serving as “diagnostic fingerprints.”

Treatment with 1,25(OH){sub 2}D{sub 3}induced HDAC2 expression and reduced NF-κB p65 expression in a rat model of OVA-induced asthma

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Zhou, Y.; Wang, G.F.; Yang, L.; Liu, F.; Kang, J.Q.; Wang, R.L.; Gu, W.; Wang, C.Y. [Department of Gerontology Medicine, Xinhua Hospital, Shanghai Jiatong University School of Medicine, Shanghai (China)

2015-04-28

Recent evidence indicates that a deficiency of 1,25-dihydroxyvitamin D{sub 3} (1,25[OH]{sub 2}D{sub 3}) may influence asthma pathogenesis; however, its roles in regulating specific molecular transcription mechanisms remain unclear. We aimed to investigate the effect of 1,25(OH){sub 2}D{sub 3} on the expression and enzyme activity of histone deacetylase 2 (HDAC2) and its synergistic effects with dexamethasone (Dx) in the inhibition of inflammatory cytokine secretion in a rat asthma model. Healthy Wistar rats were randomly divided into 6 groups: control, asthma, 1,25(OH){sub 2}D{sub 3} pretreatment, 1,25(OH){sub 2}D{sub 3} treatment, Dx treatment, and Dx and 1,25(OH){sub 2}D{sub 3} treatment. Pulmonary inflammation was induced by ovalbumin (OVA) sensitization and challenge (OVA/OVA). Inflammatory cells and cytokines in the bronchoalveolar lavage (BAL) fluid and histological changes in lung tissue were examined. Nuclear factor kappa B (NF-κB) p65 and HDAC2 expression levels were assessed with Western blot analyses and quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR). Enzyme activity measurements and immunohistochemical detection of HDAC2 were also performed. Our data demonstrated that 1,25(OH){sub 2}D{sub 3} reduced the airway inflammatory response and the level of inflammatory cytokines in BAL. Although NF-κB p65 expression was attenuated in the pretreatment and treatment groups, the expression and enzyme activity of HDAC2 were increased. In addition, 1,25(OH){sub 2}D{sub 3} and Dx had synergistic effects on the suppression of total cell infusion, cytokine release, and NF-κB p65 expression, and they also increased HDAC2 expression and activity in OVA/OVA rats. Collectively, our results indicated that 1,25(OH){sub 2}D{sub 3}might be useful as a novel HDAC2 activator in the treatment of asthma.

Disseminated peritoneal Schistosoma japonicum: a case report and review of the pathological manifestations of the helminth

International Nuclear Information System (INIS)

AlWaheeb, Salah; AlMurshed, Maryam; Dashti, Fareed; Hira Parsotam R; AlSarrafd, Lamia

2007-01-01

Schistosomiasis (also known as bilharzia, bilharziasis, bilharziosis or snail fever) is a human disease syndrome caused by infection from one of several species of parasitic trematodes of the genus Schistosoma. The three main species infecting humans are S haematobium, S japonicum, and S mansoni. S japonicum is most common in the far east, mostly in China and the Philippines. We present an unusual case of S japonicum in a 32-year-old Filipino woman who had schistosomal ova studding the peritoneal cavity and forming a mass in the right iliac fossa. (author)

Effect of praziquantel treatment during pregnancy on cytokine responses to schistosome antigens

DEFF Research Database (Denmark)

Tweyongyere, Robert; Mawa, Patrice A.; Ngom-Wegi, Sophy

2008-01-01

. Cytokine responses to S. mansoni worm and egg antigens were measured in whole blood culture before and 6 weeks after each treatment. RESULTS: Schistosome-specific cytokine responses were suppressed during pregnancy. Praziquantel treatment during pregnancy caused significant boosts in interferon-gamma (IFN......Praziquantel treatment of schistosomiasis boosts antischistosome responses, with type 2 helper T cell bias that may contribute to immunologically mediated killing and to protection against reinfection. Praziquantel treatment during pregnancy was recommended in 2002, but the immunological effects...... of the treatment had not been investigated. METHODS: A cohort of 387 Schistosoma mansoni-infected women were recruited from a larger trial of deworming during pregnancy. Women were randomized to receive either praziquantel or placebo during pregnancy. Six weeks after delivery, all women received praziquantel...

Inhibition of Asthma in OVA Sensitized Mice Model by a Traditional Uygur Herb Nepeta bracteata Benth.

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Jing Wang

2016-01-01

Full Text Available Asthma is a chronic lung inflammation which affects many people. As current therapies for asthma mainly rely on administration of glucocorticoids and have many side effects, new therapy is needed. In this study, we investigated Nepeta bracteata Benth., a traditional Uygur Herb, for its therapeutics effect in OVA induced asthmatic mice model. Treatment of OVA sensitized asthma mice with extract from Nepeta bracteata Benth. demonstrated improved lung pathology, as well as reduced infiltration of eosinophil and neutrophil. Nepeta bracteata Benth. extract also contributed to the rebalance of Th17/Treg cell via decreasing the Th17 cell and increasing the Treg, which was corresponding with the inhibited Th17 cytokine response and increased IL-10 level. Moreover, the reduced TGF-β level and Smad2/3 protein level also suggested that Nepeta bracteata Benth. extract could inhibit TGF-β mediated airway remodelling as well. Taken together, these data suggested that Nepeta bracteata Benth. may be a novel candidate for future antiasthma drug development.

Schistosome syntenin partially protects vaccinated mice against Schistosoma mansoni infection.

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Barbara C Figueiredo

2014-08-01

Full Text Available Schistosomiasis is a neglected tropical disease caused by several species of trematode of the genus Schistosoma. The disease affects more than 200 million people in the world and causes up to 280,000 deaths per year, besides having high morbidity due to chronic illness that damages internal organs. Current schistosomiasis control strategies are mainly based on chemotherapy, but many researchers believe that the best long-term strategy to control disease is a combination of drug treatment and immunization with an anti-schistosome vaccine. Among the most promising molecules as vaccine candidates are the proteins present in the tegument and digestive tract of the parasite.In this study, we describe for the first time Schistosoma mansoni syntenin (SmSynt and we evaluate its potential as a recombinant vaccine. We demonstrate by real-time PCR that syntenin is mainly expressed in intravascular life stages (schistosomula and adult worms of the parasite life cycle and, by confocal microscopy, we localize it in digestive epithelia in adult worms and schistosomula. Administration of siRNAs targeting SmSynt leads to the knock-down of syntenin gene and protein levels, but this has no demonstrable impact on parasite morphology or viability, suggesting that high SmSynt gene expression is not essential for the parasites in vitro. Mice immunization with rSmSynt, formulated with Freund's adjuvant, induces a Th1-type response, as suggested by the production of IFN-γ and TNF-α by rSmSynt-stimulated cultured splenocytes. The protective effect conferred by vaccination with rSmSynt was demonstrated by 30-37% reduction of worm burden, 38-43% reduction in the number, and 35-37% reduction in the area, of liver granulomas.Our report is the first characterization of syntenin in Schistosoma mansoni and our data suggest that this protein is a potential candidate for the development of a multi-antigen vaccine to control schistosomiasis.

Terminal Restriction Fragment Length Polymorphism for the Identification of Spirorchiid Ova in Tissues from the Green Sea Turtle, Chelonia mydas.

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Phoebe A Chapman

Full Text Available Blood flukes are among the most common disease causing pathogens infecting vertebrates, including humans and some of the world's most globally endangered fauna. Spirorchiid blood flukes are parasites of marine turtles, and are associated with pathology, strandings and mortalities worldwide. Their ova embolize in tissues and incite significant inflammatory responses, however attempts to draw correlations between species and lesions are frustrated by difficulties in identifying ova beyond the genus level. In this study, a newly developed terminal restriction fragment length polymorphism (T-RFLP method was validated as a tool for differentiating between mixed spirorchiid ova in turtle tissue. Initially, a multiplex PCR was used to differentiate between the five genera of spirorchiid flukes. Following this, PCR was performed using genus/genera-specific fluorescently tagged primer pairs and PCR products digested analysis using restriction endonucleases. Using capillary electrophoresis, this T-RFLP method could differentiate between twelve species and genotypes of spirorchiid flukes in turtles. It was applied to 151 tissue samples and successfully identified the spirorchiid species present. It was found to be more sensitive than visual diagnosis, detecting infections in 28 of 32 tissues that were negative on histology. Spirorchiids were present in 96.7% of tissues tested, with Neospirorchis genotype 2 being the most prevalent, present in 93% of samples. Mixed infections were common, being present in 60.7% of samples tested. The method described here is, to our knowledge, the first use of the T-RFLP technique on host tissues or in an animal ecology context, and describes a significant advancement in the clinical capacity to diagnose a common cause of illness in our environment. It is proven as a sensitive, specific and cost-efficient means of identifying spirorchiid flukes and ova in turtles, with the potential to contribute valuable information to

[Comparative observation on inhibition of hemozoin formation and their in vitro and in vivo anti-schistosome activity displayed by 7 antimalarial drugs].

Science.gov (United States)

Xue, Jian; Jiang, Bin; Liu, Cong-Shan; Sun, Jun; Xiao, Shu-Hua

2013-06-01

To observe and compare the inhibition of hemozoin formation and the in vitro as well as in vivo antischistosomal activity induced by seven antimalarial drugs. Inhibition of hemozoin formation displayed by chloroquine phosphate, quinine hydrochloride, quinidine, mefloquine hydrochloride, pyronaridine phosphate and lumefantrine at 25 micromol/L, and artemether at 100 micromol/L was performed by assay of inhibition of beta-hematin formation in 1 mol/L sodium acetate buffers containing hematin with various pH of 4.0, 4.2, 4.4, 4.6, 4.8, and 5.0. In in vitro antischistosomal study, the medium of RPMI 1640 supplemented by 10% calf serum was used to maintain the adult Schistosoma japonicum, and the 50% and 95% lethal concentrations (LC50 and LC95) to kill the adult worms of each drug were then determined. Meanwhile, the interaction of quinine, pyronaridine and chloroquine combined with hemin against adult schistosomes was also undertaken. As to in vivo test, the efficacy of seven antimalarial drugs administered orally or intraperitoneally to mice infected with adult schistosomes was observed. In the acidic acetate-hematin solution, 25 micromol/L pyronaridine showed significant inhibition of beta-hematin formation at pH 4.4-5.0 with inhibition rates of 81.3%-97.0%. At pH 4.6, the inhibition rates of beta-hematin formation in acetate-hematin solution induced by mefloquine, chloroquine or quinine at concentration of 25 beta mol/L were 79.7%, 72.8% or 65.8%, respectively, and the beta-hematin formation was continually inhibited by these 3 antimalarial drugs at pH 4.8 and 5.0 with inhibition rates of 83.1%-90.6%, 41.9%-49.0% or 53.2-62.0%. The inhibition rates of beta-hematin formation at pH 4.6 and 4.8-5.0 induced by lumefantrine 25 micromol/L were 74.3% and 40.4%-40.5%, respectively. While under the same concentration of quinidine, 53.4% and 50.9% inhibition rates of beta-hematin formation were observed at pH 4.8 and 5.0. As to artemether, higher concentration of 100

Current progress in the development and use of artemether for chemoprophylaxis of major human schistosome parasites.

Science.gov (United States)

Utzinger, J; Xiao, S; Keiser, J; Chen, M; Zheng, J; Tanner, M

2001-12-01

Human schistosomiasis, a chronic and debilitating parasitic disease of the tropics, is ranked second after malaria in terms of public health importance. At present, there is no vaccine available, and chemotherapy is the cornerstone of schistosomiasis control. Praziquantel is the drug of choice. Oxamniquine has become difficult to obtain and metrifonate has recently been withdrawn from the market. Rapid re-infection following treatment and concern about praziquantel resistance called for the search of novel drugs for prevention and cure of schistosomiasis. Significant progress has been made with artemether, the methyl ether of dihydroartemisinin, already widely used for the treatment of malaria. The present article reviews the literature that led to the development of artemether for chemoprophylaxis in schistosomiasis, and it summarises the experiences so far obtained with its use to control schistosomiasis in different endemic settings. Topics covered include an overview of the global burden of schistosomiasis and approaches for its control; the nature and features of artemisinin and related derivatives, initially discovered as antimalarials, other bioactivities, and their recent discovery of antischistosomal properties; a historic account disclosing the antischistosomal activity of artemether; in vivo assessment of drug susceptibility of different developmental stages of schistosome parasites; artemether-induced pathology evidenced by scanning and transmission electron microscopy; the possible mechanism of action; in vivo studies with combination therapy of artemether and praziquantel; results of randomised controlled clinical trials of oral artemether for the prevention of patent infection and morbidity; and, ultimately the translation of this knowledge into public health action in different endemic settings towards a more integrated approach of schistosomiasis control.

The susceptibility of Marisa cornuarietis, a predator of schistosome bearing snails, to N-tritylmorpholine.

Science.gov (United States)

Meier-Brook, C; Tjhen, K Y

1977-03-01

Introduction of the ampullariid snail, Marisa cornuarietis (L.), into water treated with molluscicides, in order to secure the success of chemical control of schistosome host snails, is promising. Adult Marisa can be introduced only two days after treating water of pH less than or equal to 7-9 with N-tritylmorpholine (= FresconR Shell) at a concentration of 0-03 ppm. There is considerable variation in the susceptibility of different strains: the LT50 in a concentration of 0-03 ppm Frescon at 25 degrees C was about 27-3 hours for a Puerto Rican and 44-6 hours for a Floridan strain, both 52 weeks old. At sexual maturity, i.e. approximately 18 weeks at 25 degrees C, the LT50 for the Floridan strain was approximately 31-8 hours; experiments with a hybrid stock of the two strains had an LT50 of 30-0 hours. Younger snails were significantly more susceptible to the molluscicide, and eggs were approximately four times more resistant than adults; this agrees with findings by previous authors for other snail species. In the case of the accidental uncontrolled spread of Marisa to cultivated areas it is suggested that a concentration of 0-03 Frescon is applied for at least four days.

Rigidity and resistance of larval- and adult schistosomes-medium interface

Energy Technology Data Exchange (ETDEWEB)

Migliardo, Federica, E-mail: fmigliardo@unime.it [Department of Physics and Earth Sciences, University of Messina, 98166 Messina (Italy); Tallima, Hatem; El Ridi, Rashika [Zoology Department, Faculty of Science, Cairo University, Cairo 12613 (Egypt)

2014-03-28

Graphical abstract: - Highlights: • Schistosoma larvae and worms are studied by neutron scattering. • Measurements on larvae were repeated after one day and by increasing temperature. • The flexibility properties of larvae and adult parasites are compared. • The parasite rigidity is related to their resistance to the hostile environment. • Insight into the parasite defense mechanisms to the immune system attack is achieved. - Abstract: Schistosomiasis is second only to malaria in prevalence and severity, and is still a major health problem in many tropical countries worldwide with about 200–300 million cases and with more than 800 million people at risk of infection. Based on these data, the World Health Organization recommends fostering research efforts for understanding at any level the mechanisms of the infection and then decreasing the social and economical impact of schistosomiasis. A key role is played by the parasite apical lipid membrane, which is entirely impervious to the surrounding elements of the immune system. We have previously demonstrated that the interaction between schistosomes and surrounding medium is governed by a parasite surface membrane sphingomyelin-based hydrogen barrier. In the present article, the elastic contribution to the total motion as a function of the exchanged wave-vector Q and the mean square displacement values for Schistosoma mansoni larvae and worms and Schistosomahaematobium worms have been evaluated by quasi elastic neutron scattering (QENS). The results point out that S. mansoni larvae show a smaller mean square displacement in comparison to S. mansoni and S. haematobium worms. These values increased by repeating the measurements after one day. These differences, which are analogous to those observed for the diffusion coefficient we previously evaluated, are interpreted in terms of rigidity of the parasite-medium interaction. S. mansoni larvae are the most rigid systems, while S. haematobium worms are the most

Guidelines for the diagnosis and treatment of schistosomal myeloradiculopathy Orientações sobre o diagnóstico e tratamento da mielorradiculopatia associada à esquistossomose

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José Roberto Lambertucci

2007-10-01

Full Text Available Schistosomal myeloradiculopathy is the most severe and disabling ectopic form of Schistosoma mansoni infection. The prevalence of SMR in centres in Brazil and Africa that specialise in attending patients with non traumatic myelopathy is around 5%. The initial signs and symptoms of the disease include lumbar and/or lower limb pain, paraparesis, urinary and intestinal dysfunctions, and impotence in men. The cerebrospinal fluid of SMR patients shows an increase in protein concentration and in the number of mononuclear cells in 90% of cases; eosinophils have been reported in 40%. The use of magnetic resonance imaging is particularly valuable in the diagnosis of Schistosomal myeloradiculopathy. The exclusion of other myelopathies and systemic diseases remains mandatory. Early diagnosis and treatment with steroids and schistosomicides provide a cure for most patients, whilst delayed treatment can result in irreversible physical disabilities or death. To improve awareness concerning Schistosomal myeloradiculopathy amongst public health professionals, and to facilitate the control of the disease, the Brazilian Ministry of Health has launched a program of education and control of this ectopic form of schistosomiasis. The present paper reviews current methods for the diagnosis of SMR and outlines protocols for treatment of the disease.A mielorradiculopatia esquistossomótica é a forma ectópica mais grave da infecção pelo Schistosoma mansoni. A prevalência da mielorradiculopatia esquistossomótica em centros médicos no Brasil e em África, especializados no atendimento de pacientes com mielopatia, encontra-se em torno de 5%. Os sintomas e sinais iniciais da doença incluem: dor lombar e/ou dor em membros inferiores, paraparesia, disfunções urinária e intestinal, e impotência no homem. A análise do líqüor destes pacientes revela aumento na concentração de proteínas e no número de células mononucleares em 90% dos casos; a presença de eosin

Determination the lethal dose of ascaris lumbricoides ova by gamma irradiation

International Nuclear Information System (INIS)

Shamma, M.; Al-Adawi, M.; Sharabi, N.

2002-11-01

The lethal gamma irradiation dose of ascaris lumbricoides which collected from Damascus Sewage water Plant was determined. Ascaris lumbricoides ova were treated with several gamma irradiation doses with (0.1, 0.2, 0.3, 0.4,...and 1.5 KGy). No morphological changes were observed on the eggs when directly examined microscopically after irradiation. However after two weeks of incubation at 37 degree centigrade the cell contents of the eggs which irradiated with 0.5 KGy and beyond were fragmented and scattered in the whole eggs and no larvae were observed after eight weeks of incubation. It is concluded that the dose 0.5 my be considered as the dose of choice if sewage water is to be treated by gamma rays. (author)

Determination the lethal dose of ascaris lumbricoides ova by gamma irradiation

CERN Document Server

Shamma, M A; Sharabi, N

2002-01-01

The lethal gamma irradiation dose of ascaris lumbricoides which collected from Damascus Sewage water Plant was determined. Ascaris lumbricoides ova were treated with several gamma irradiation doses with (0.1, 0.2, 0.3, 0.4,...and 1.5 KGy). No morphological changes were observed on the eggs when directly examined microscopically after irradiation. However after two weeks of incubation at 37 degree centigrade the cell contents of the eggs which irradiated with 0.5 KGy and beyond were fragmented and scattered in the whole eggs and no larvae were observed after eight weeks of incubation. It is concluded that the dose 0.5 my be considered as the dose of choice if sewage water is to be treated by gamma rays.

School Water, Sanitation, and Hygiene, Soil-Transmitted Helminths, and Schistosomes: National Mapping in Ethiopia.

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Jack E T Grimes

2016-03-01

Full Text Available It is thought that improving water, sanitation, and hygiene (WASH might reduce the transmission of schistosomes and soil-transmitted helminths, owing to their life cycles. However, few large-scale studies have yet assessed the real extent of associations between WASH and these parasites.In the 2013-2014 Ethiopian national mapping of infections with these parasites, school WASH was assessed alongside infection intensity in children, mostly between 10 and 15 years of age. Scores were constructed reflecting exposure to schistosomes arising from water collection for schools, from freshwater sources, and the adequacy of school sanitation and hygiene facilities. Kendall's τb was used to test the WASH scores against the school-level arithmetic mean intensity of infection with each parasite, in schools with at least one child positive for the parasite in question. WASH and parasitology data were available for 1,645 schools. More frequent collection of water for schools, from open freshwater sources was associated with statistically significantly higher Schistosoma mansoni infection intensity (Kendall's τb = 0.097, 95% confidence interval, CI: 0.011 to 0.18, better sanitation was associated with significantly lower Ascaris lumbricoides intensity (Kendall's τb = -0.067, 95% CI: -0.11 to -0.023 and borderline significant lower hookworm intensity (Kendall's τb = -0.039, 95% CI: -0.090 to 0.012, P = 0.067, and better hygiene was associated with significantly lower hookworm intensity (Kendall's τb = -0.076, 95% CI: -0.13 to -0.020. However, no significant differences were observed when comparing sanitation and infection with S. mansoni or Trichuris trichiura, or hygiene and infection with A. lumbricoides or T. trichiura.Improving school WASH may reduce transmission of these parasites. However, different forms of WASH appear to have different effects on infection with the various parasites, with our analysis finding the strongest associations between

School Water, Sanitation, and Hygiene, Soil-Transmitted Helminths, and Schistosomes: National Mapping in Ethiopia.

Science.gov (United States)

Grimes, Jack E T; Tadesse, Gemechu; Mekete, Kalkidan; Wuletaw, Yonas; Gebretsadik, Abeba; French, Michael D; Harrison, Wendy E; Drake, Lesley J; Gardiner, Iain A; Yard, Elodie; Templeton, Michael R

2016-03-01

It is thought that improving water, sanitation, and hygiene (WASH) might reduce the transmission of schistosomes and soil-transmitted helminths, owing to their life cycles. However, few large-scale studies have yet assessed the real extent of associations between WASH and these parasites. In the 2013-2014 Ethiopian national mapping of infections with these parasites, school WASH was assessed alongside infection intensity in children, mostly between 10 and 15 years of age. Scores were constructed reflecting exposure to schistosomes arising from water collection for schools, from freshwater sources, and the adequacy of school sanitation and hygiene facilities. Kendall's τb was used to test the WASH scores against the school-level arithmetic mean intensity of infection with each parasite, in schools with at least one child positive for the parasite in question. WASH and parasitology data were available for 1,645 schools. More frequent collection of water for schools, from open freshwater sources was associated with statistically significantly higher Schistosoma mansoni infection intensity (Kendall's τb = 0.097, 95% confidence interval, CI: 0.011 to 0.18), better sanitation was associated with significantly lower Ascaris lumbricoides intensity (Kendall's τb = -0.067, 95% CI: -0.11 to -0.023) and borderline significant lower hookworm intensity (Kendall's τb = -0.039, 95% CI: -0.090 to 0.012, P = 0.067), and better hygiene was associated with significantly lower hookworm intensity (Kendall's τb = -0.076, 95% CI: -0.13 to -0.020). However, no significant differences were observed when comparing sanitation and infection with S. mansoni or Trichuris trichiura, or hygiene and infection with A. lumbricoides or T. trichiura. Improving school WASH may reduce transmission of these parasites. However, different forms of WASH appear to have different effects on infection with the various parasites, with our analysis finding the strongest associations between water and S

Single classifier, OvO, OvA and RCC multiclass classification method in handheld based smartphone gait identification

Science.gov (United States)

Raziff, Abdul Rafiez Abdul; Sulaiman, Md Nasir; Mustapha, Norwati; Perumal, Thinagaran

2017-10-01

Gait recognition is widely used in many applications. In the application of the gait identification especially in people, the number of classes (people) is many which may comprise to more than 20. Due to the large amount of classes, the usage of single classification mapping (direct classification) may not be suitable as most of the existing algorithms are mostly designed for the binary classification. Furthermore, having many classes in a dataset may result in the possibility of having a high degree of overlapped class boundary. This paper discusses the application of multiclass classifier mappings such as one-vs-all (OvA), one-vs-one (OvO) and random correction code (RCC) on handheld based smartphone gait signal for person identification. The results is then compared with a single J48 decision tree for benchmark. From the result, it can be said that using multiclass classification mapping method thus partially improved the overall accuracy especially on OvO and RCC with width factor more than 4. For OvA, the accuracy result is worse than a single J48 due to a high number of classes.

Andrographolide ameliorates OVA-induced lung injury in mice by suppressing ROS-mediated NF-κB signaling and NLRP3 inflammasome activation.

Science.gov (United States)

Peng, Shuang; Gao, Jian; Liu, Wen; Jiang, Chunhong; Yang, Xiaoling; Sun, Yang; Guo, Wenjie; Xu, Qiang

2016-12-06

In this study, we attempted to explore the effect and possible mechanism of Andrographolide on OVA-induced asthma. OVA challenge induced significant airway inflammatory cell recruitment and lung histological alterations, which were ameliorated by Andrographolide. The protein levels of cytokines in bron-choalveolar fluid (BALF) and serum were reduced by Andrographolide administration as well as the mRNA levels in lung tissue. Mechanically, Andrographolide markedly hampered the activation of nuclear factor-κB (NF-κB) and NLRP3 inflammasome both in vivo and vitro thus decreased levels of TNF-α and IL-1β. Finally, we confirmed that ROS scavenging was responsible for Andrographolide's inactivation of NF-κB and NLRP3 inflammasome signaling. Our study here revealed the effect and possible mechanism of Andrographolide on asthma, which may represent a new therapeutic approach for treating this disease.

Clinical-epidemiologic profile of the schistosomal myeloradiculopathy in Pernambuco, Brazil

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Karina Conceição GM de Araújo

2010-07-01

Full Text Available This was a retrospective descriptive study on a series of cases of schistosomal myeloradiculopathy (SMR and the aim was to investigate the incidence of this disease and its clinical and epidemiological characteristics in cases diagnosed at three healthcare units in Pernambuco, Brazil between 1994-2006. The data were collected by reviewing the medical records from both the neurological and paediatric outpatient clinics and wards of the Hospital Clinics, Hospital of the Restoration and Pernambuco Mother and Child Institute. To gather the data, a spinal cord schistosomiasis evaluation protocol was used. The diagnoses were based on positive epidemiological evidence of schistosomiasis, clinical findings and laboratory tests (stool parasitological examination or rectal biopsies, magnetic resonance imaging findings and cerebrospinal fluid investigations. A total of 139 cases aged between 2-83 years were found. The most important determinants of SMR were male sex (66.2%, contact with fresh water (91%, origin in endemic regions (39.5%, lower-limb muscle weakness (100%, sensory level at the lower thoracic medulla (40.3%, myeloradicular form (76% and presence of eggs in the stool parasitological examination (48%. This sample indicates the need for intervention policies guided by diagnostic standardization, thereby avoiding disease under-notification.

Portal blood flow volume measurement in schistosomal patients: evaluation of Doppler ultrasonography reproducibility

International Nuclear Information System (INIS)

Leao, Alberto Ribeiro de Souza; Santos, Jose Eduardo Mourao; Moulin, Danilo Sales; Shigueoka, David Carlos; D'Ippolito, Giuseppe; Colleoni, Ramiro

2008-01-01

Objective: To evaluate the reproducibility of Doppler ultrasonography in the measurement of portal blood flow volume in schistosomal patients. Materials and methods: Prospective, transversal, observational and self-paired study evaluating 21 patients with hepatosplenic schistosomiasis submitted to Doppler ultrasonography performed by three independent observers for measurement of portal blood flow. Pairwise interobserver agreement was calculated by means of the intraclass correlation coefficient, paired t-test and Pearson's correlation coefficient. Results: Interobserver agreement was excellent. Intraclass correlation ranged from 80.6% to 93.0% (IC at 95% [65.3% ; 95.8%]), with the Pearson's correlation coefficient ranging between 81.6% and 92.7% with no statistically significant interobserver difference regarding the mean portal blood flow volume measured by Doppler ultrasonography (p = 0.954 / 0.758 / 0.749). Conclusion: Doppler ultrasonography has demonstrated to be a reliable method for measuring the portal blood flow volume in patients with portal hypertension secondary to schistosomiasis, with a good interobserver agreement. (author)

Portal blood flow volume measurement in schistosomal patients: evaluation of Doppler ultrasonography reproducibility

Energy Technology Data Exchange (ETDEWEB)

Leao, Alberto Ribeiro de Souza; Santos, Jose Eduardo Mourao; Moulin, Danilo Sales; Shigueoka, David Carlos; D' Ippolito, Giuseppe [Universidade Federal de Sao Paulo (UNIFESP/EPM), SP (Brazil). Escola Paulista de Medicina. Dept. de Diagnostico por Imagem]. E-mail: ar.leao@uol.com.br; Colleoni, Ramiro [Universidade Federal de Sao Paulo (UNIFESP/EPM), SP (Brazil). Escola Paulista de Medicina. Dept. de Gastroenterologia

2008-09-15

Objective: To evaluate the reproducibility of Doppler ultrasonography in the measurement of portal blood flow volume in schistosomal patients. Materials and methods: Prospective, transversal, observational and self-paired study evaluating 21 patients with hepatosplenic schistosomiasis submitted to Doppler ultrasonography performed by three independent observers for measurement of portal blood flow. Pairwise interobserver agreement was calculated by means of the intraclass correlation coefficient, paired t-test and Pearson's correlation coefficient. Results: Interobserver agreement was excellent. Intraclass correlation ranged from 80.6% to 93.0% (IC at 95% [65.3% ; 95.8%]), with the Pearson's correlation coefficient ranging between 81.6% and 92.7% with no statistically significant interobserver difference regarding the mean portal blood flow volume measured by Doppler ultrasonography (p = 0.954 / 0.758 / 0.749). Conclusion: Doppler ultrasonography has demonstrated to be a reliable method for measuring the portal blood flow volume in patients with portal hypertension secondary to schistosomiasis, with a good interobserver agreement. (author)

Late Bronze Age in Alcáçova de Santarém (Portugal

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Arruda, Ana Margarida

2015-06-01

Full Text Available The field work that took place in the restaurant area in Jardim das Portas do Sol (Alcáçova de Santarém recovered well-preserved archaeological layers dated to the Late Bronze Age, lying directly underneath the Iron Age phase. The excavation made it possible to collect an important set of ceramics that incorporate printed and incised decoration, which can be easily decoration related to the Cogotas 1 cultural background. Burnished decorations, with grooves on the inner surface and outer strips, are less common. The formal repertoire does not deviate from what is known about the Late Bronze Age in central and southern Iberian Peninsula. The data allow us to propose a chronology centered in the early 1st millennium BCE for this occupation.Durante los trabajos de campo, realizados en el área del restaurante del Jardim das Portas do Sol, se documentaron, por primera vez en Alcáçova de Santarém, niveles conservados del final de la Edad del Bronce, inmediatamente infrapuestos a los de la Edad del Hierro. Su excavación permitió recoger un conjunto de materiales cerámicos que incorpora varios fragmentos decorados por impresión e incisión, que pueden ser fácilmente relacionados con el universo cultural de Cogotas 1. Las decoraciones bruñidas con surcos en la superficie interna y con franjas al exterior son mucho menos frecuentes. El repertorio formal no difiere del conocido para el Bronce Final del centro y sur de la Península Ibérica. Los datos permiten proponer una cronologia del inicio del 1 milenio a.n.e. (siglo IX para esta ocupación.

Pharmacological profiling an abundantly expressed schistosome serotonergic GPCR identifies nuciferine as a potent antagonist

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John D. Chan

2016-12-01

Full Text Available 5-hydroxytryptamine (5-HT is a key regulator of muscle contraction in parasitic flatworms. In Schistosoma mansoni, the myoexcitatory action of 5-HT is effected through activation of a serotonergic GPCR (Sm.5HTRL, prioritizing pharmacological characterization of this target for anthelmintic drug discovery. Here, we have examined the effects of several aporphine alkaloids on the signaling activity of a heterologously expressed Sm.5HTRL construct using a cAMP biosensor assay. Four structurally related natural products – nuciferine, D-glaucine, boldine and bulbocapnine – were demonstrated to block Sm.5HTRL evoked cAMP generation with the potency of GPCR blockade correlating well with the ability of each drug to inhibit contractility of schistosomule larvae. Nuciferine was also effective at inhibiting both basal and 5-HT evoked motility of adult schistosomes. These data advance our understanding of structure-affinity relationships at Sm.5HTRL, and demonstrate the effectiveness of Sm.5HTRL antagonists as hypomotility-evoking drugs across different parasite life cycle stages.

Three-dimensional structure of a schistosome serpin revealing an unusual configuration of the helical subdomain

Energy Technology Data Exchange (ETDEWEB)

Granzin, Joachim [Institute of Complex Systems, ICS-6: Structural Biochemistry, Forschungszentrum Jülich, 52425 Jülich (Germany); Huang, Ying; Topbas, Celalettin [Department of Cell Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195 (United States); Huang, Wenying [Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195 (United States); Wu, Zhiping [Department of Cell Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195 (United States); Misra, Saurav [Department of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195 (United States); Hazen, Stanley L. [Department of Cell Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195 (United States); Blanton, Ronald E. [Department of Infectious Diseases, Case Western Reserve University, Cleveland, OH 44190 (United States); Lee, Xavier [Department of Cell Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195 (United States); Weiergräber, Oliver H., E-mail: o.h.weiergraeber@fz-juelich.de [Institute of Complex Systems, ICS-6: Structural Biochemistry, Forschungszentrum Jülich, 52425 Jülich (Germany)

2012-06-01

The crystal structure of ShSPI, a serpin from the blood fluke S. haematobium, reveals some peculiar features of the helical subdomain which have not been observed previously in the serpin superfamily. Parasitic organisms are constantly challenged by the defence mechanisms of their respective hosts, which often depend on serine protease activities. Consequently, protease inhibitors such as those belonging to the serpin superfamily have emerged as protective elements that support the survival of the parasites. This report describes the crystal structure of ShSPI, a serpin from the trematode Schistosoma haematobium. The protein is exposed on the surface of invading cercaria as well as of adult worms, suggesting its involvement in the parasite–host interaction. While generally conforming to the well established serpin fold, the structure reveals several distinctive features, mostly concerning the helical subdomain of the protein. It is proposed that these peculiarities are related to the unique biological properties of a small serpin subfamily which is conserved among pathogenic schistosomes.

The monomeric orphan nuclear receptor Schistosoma mansoni Ftz-F1 dimerizes specifically and functionally with the schistosome RXR homologue, SmRXR1

International Nuclear Information System (INIS)

Bertin, Benjamin; Caby, Stephanie; Oger, Frederik; Sasorith, Souphatta; Wurtz, Jean-Marie; Pierce, Raymond J.

2005-01-01

In an attempt to understand development and differentiation processes of the parasitic blood fluke Schistosoma mansoni, several members of the nuclear receptor superfamily were cloned, including SmFtz-F1 (S. mansoni Fushi Tarazu-factor 1). The Ftz-F1 nuclear receptor subfamily only contains orphan receptors that bind to their response element as monomers. Whereas SmFtz-F1 displays these basic functional properties, we have identified an original and specific interaction between SmFtz-F1 and the schistosome RXR homologue, SmRXR1. The mammalian two-hybrid assay showed that the D, E, and F domains of SmFtz-F1 were capable of interacting specifically with the E domain of SmRXR1 but not with that of mouse RXRα. Using three-dimensional LBD homology modelling and structure-guided mutagenesis, we were able to demonstrate the essential role of exposed residues located in the dimerization interfaces of both receptors in the maintenance of the interaction. Cotransfection experiments with constructions encoding full-length nuclear receptors show that SmRXR1 potentiates the transcriptional activity of SmFtz-F1 from various promoters. Nevertheless, the lack of identification of a dimeric response element for this SmFtz-F1/SmRXR1 heterodimer seems to indicate a 'tethering' mechanism. Thus, our results suggest for the first time that a member of the Ftz-F1 family could heterodimerize functionally with a homologue of the universal heterodimerization partner of nuclear receptors. This unique property confirms that SmFtz-F1 may be involved in the development and differentiation of schistosome-specific structures

Differences in the gene expression profiles of haemocytes from schistosome-susceptible and -resistant biomphalaria glabrata exposed to Schistosoma mansoni excretory-secretory products.

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Zahida Zahoor

Full Text Available During its life cycle, the helminth parasite Schistosoma mansoni uses the freshwater snail Biomphalaria glabrata as an intermediate host to reproduce asexually generating cercariae for infection of the human definitive host. Following invasion of the snail, the parasite develops from a miracidium to a mother sporocyst and releases excretory-secretory products (ESPs that likely influence the outcome of host infection. To better understand molecular interactions between these ESPs and the host snail defence system, we determined gene expression profiles of haemocytes from S. mansoni-resistant or -susceptible strains of B. glabrata exposed in vitro to S. mansoni ESPs (20 μg/ml for 1 h, using a 5K B. glabrata cDNA microarray. Ninety-eight genes were found differentially expressed between haemocytes from the two snail strains, 57 resistant specific and 41 susceptible specific, 60 of which had no known homologue in GenBank. Known differentially expressed resistant-snail genes included the nuclear factor kappa B subunit Relish, elongation factor 1α, 40S ribosomal protein S9, and matrilin; known susceptible-snail specific genes included cathepsins D and L, and theromacin. Comparative analysis with other gene expression studies revealed 38 of the 98 identified genes to be uniquely differentially expressed in haemocytes in the presence of ESPs, thus identifying for the first time schistosome ESPs as important molecules that influence global snail host-defence cell gene expression profiles. Such immunomodulation may benefit the schistosome, enabling its survival and successful development in the snail host.

Comparison of four species of snails as potential decoys to intercept schistosome miracidia.

Science.gov (United States)

Laracuente, A; Brown, R A; Jobin, W

1979-01-01

Preliminary studies have shown that various species of aquatic snails may be used as decoys or "sponges" to intercept schistosome miracidia, thereby preventing the miracidia from reaching the snails which normally serve as their intermediate host. In this study, four species of snails were evaluated as candidate decoys for field trials: Marisa cornuarietis, Pomacea australis, Helisoma caribaeum, and Tarebia granifera. In the laboratory all four species caused considerable reductions in the proportion of Biomphalaria glabrata infected by miracidia of Schistosoma mansoni. The most effective decoys were M. cornuarietis and H. caribaeum, both of which caused experimental infection levels of 90% to decrease to 25% when five decoy snails were present for each target snail. When ten decoy snails were present for each target snail, the proportion infected decreased to 1%. M. cornuarietis was chosen as the candidate for field trials because it was found more frequently in Puerto Rico than was H. caribaeum. Initial field trials in two ponds showed that M. cornuarietis blocked infections at a ratio of 6 decoys to 1 target snail, confirming the laboratory results. Further studies in flowing water are needed before the technique can be generally evaluated in an endemic area.

In vivo micro-CT assessment of airway remodeling in a flexible OVA-sensitized murine model of asthma.

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Mathieu Lederlin

Full Text Available Airway remodeling is a major pathological feature of asthma. Up to now, its quantification still requires invasive methods. In this study, we aimed at determining whether in vivo micro-computed tomography (micro-CT is able to demonstrate allergen-induced airway remodeling in a flexible mouse model of asthma. Sixty Balb/c mice were challenged intranasally with ovalbumin or saline at 3 different endpoints (Days 35, 75, and 110. All mice underwent plethysmography at baseline and just prior to respiratory-gated micro-CT. Mice were then sacrificed to assess bronchoalveolar lavage and lung histology. From micro-CT images (voxel size = 46×46×46 µm, the numerical values of total lung attenuation, peribronchial attenuation (PBA, and PBA normalized by total lung attenuation were extracted. Each parameter was compared between OVA and control mice and correlation coefficients were calculated between micro-CT and histological data. As compared to control animals, ovalbumin-sensitized mice exhibited inflammation alone (Day 35, remodeling alone (Day 110 or both inflammation and remodeling (Day 75. Normalized PBA was significantly greater in mice exhibiting bronchial remodeling either alone or in combination with inflammation. Normalized PBA correlated with various remodeling markers such as bronchial smooth muscle size or peribronchial fibrosis. These findings suggest that micro-CT may help monitor remodeling non-invasively in asthmatic mice when testing new drugs targeting airway remodeling in pre-clinical studies.

Full scale validation of helminth ova (Ascaris suum) inactivation by different sludge treatment processes

Energy Technology Data Exchange (ETDEWEB)

Paulsrud, B.; Gjerde, B.; Lundar, A.

2003-07-01

The Norwegian sewage sludge regulation requires disinfection (hygienisation) of all sludges for land application, and one of the criteria is that disinfected sludge should not contain viable helminth ova. All disinfection processes have to be designed and operated in order to comply with this criteria, and four processes employed in Norway (thermophilic aerobic pre-treatment, pre-pasteurisation, thermal vacuum drying in membrane filter presses and lime treatment) have been tested in full scale by inserting semipermeable bags of Ascaris suum eggs into the processes for certain limes. For lime treatment supplementary laboratory tests have been conducted. The paper presents the results of the experiments, and it could be concluded that all processes, except lime treatment, could be operated at less stringent time-temperature regimes than commonly experienced at Norwegian plants today. (author)

Oral Treatment with Extract of Agaricus blazei Murill Enhanced Th1 Response through Intestinal Epithelial Cells and Suppressed OVA-Sensitized Allergy in Mice

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Go Bouike

2011-01-01

Full Text Available To clarify the mechanism of the antiallergic activity of Agaricus blazei Murill extract (ABME, the present paper used an in vivo allergy model and an in vitro intestinal gut model. During OVA sensitization, the serum IgE levels decreased significantly in ABME group. Interleukin (IL-4 and -5 produced from OVA-restimulated splenocytes was significantly decreased, and anti-CD3ε/CD28 antibody treatment also reduced IL-10, -4, and -5 production and increased IFN-γ production in ABME group. These results suggest that oral administration of ABME improves Th1/Th2 balance. Moreover, a coculture system constructed of Caco-2 cells and splenocytes from OT-II mice or RAW 264.7 cells indicated that the significant increases in IFN-γ production by ABME treatment. Therefore, it was concluded that the antiallergic activity of ABME was due to the activation of macrophages by epithelial cells and the promotion of the differentiation of naïve T cells into Th1 cells in the immune.

Immune responses and parasitological observations induced during probiotic treatment with medicinal Trichuris suis ova in a healthy volunteer

DEFF Research Database (Denmark)

Williams, Andrew R; Dige, Anders; Rasmussen, Tue Kruse

2017-01-01

Ingestion of eggs (ova) of the porcine nematode parasite Trichuris suis (TSO) may reduce the severity of autoimmune disorders, however the development of TSO treatment as a useful therapy for autoimmune diseases is hampered by a lack of knowledge on the development of the parasite and the nature...... was also reflected to some extent in the peripheral circulation. These results, together with the first definitive observations that T. suis can mature to adult size and reproduce in humans, shed new light on the interaction between the human immune system and probiotic helminth treatment, which should...

The schistosome oesophageal gland: initiator of blood processing.

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Xiao-Hong Li

Full Text Available BACKGROUND: Although the ultrastructure of the schistosome esophageal gland was described >35 years ago, its role in the processing of ingested blood has never been established. The current study was prompted by our identification of MEG-4.1 expression in the gland and the observation of erythrocyte uncoating in the posterior esophagus. METHODOLOGY/PRINCIPAL FINDINGS: The salient feature of the posterior esophagus, characterized by confocal and electron microscopy, is the enormous increase in membrane surface area provided by the plate-like extensions and basal invaginations of the lining syncytium, with unique crystalloid vesicles releasing their contents between the plates. The feeding process was shown by video microscopy to be divided into two phases, blood first accumulating in the anterior lumen before passing as a bolus to the posterior. There it streamed around a plug of material revealed by confocal microscopy as tethered leucocytes. These were present in far larger numbers than predicted from the volume of the lumen, and in varying states of damage and destruction. Intact erythrocytes were detected in the anterior esophagus but not observed thereafter, implying that their lysis occurred rapidly as they enter the posterior. Two further genes, MEGs 4.2 and 14, were shown to be expressed exclusively in the esophageal gland. Bioinformatics predicted that MEGs 4.1 and 4.2 possessed a common hydrophobic region with a shared motif, while antibodies to SjMEG-4.1 showed it was bound to leucocytes in the esophageal lumen. It was also predicted that MEGs 4.1 and 14 were heavily O-glycosylated and this was confirmed for the former by 2D-electrophoresis and Western blotting. CONCLUSIONS/SIGNIFICANCE: The esophageal gland and its products play a central role in the processing of ingested blood. The binding of host antibodies in the esophageal lumen shows that some constituents are antibody targets and could provide a new source of vaccine candidates.

Characteristic features of computed tomography (CT) in hepatic schistosomiasis japonica

Energy Technology Data Exchange (ETDEWEB)

Sakemi, Taisuke; Sakai, Terufumi; Majima, Yasuo [Kurume Univ., Fukuoka (Japan). School of Medicine

1984-06-01

Characteristic finding of CT in the liver of hepatic schistosomiasis japonica were compared with histological changes. The study was made on 7 cases with schistosomatic liver cirrhosis (SLC) and 7 SLC cases with hepatocellular carcinoma (HCC). Characteristic CT findings were high density funicular patterns showing turtle shell appearance (4 cases), high density spotty patterns (3 cases) and both mixed patterns (7 cases). These patterns were not changed by contrast medium study. Funicular and mixed patterns were observed in both lobes of the liver, however, spotty patterns were seen only in the right lobe. It was difficult to distinguish liver tissue surrounded by funicular patterns from HCC lesion. Histopathological study of autopsied livers and CT scanning of thin cut livers revealed that high density funicular patterns represent deposits of calcified schistosomal ova in the fibrous septa.

Parasites in soil/sludge systems

Energy Technology Data Exchange (ETDEWEB)

Brandon, J.R.

1978-03-01

The potential for the transmission of parasites, such as Entamoeba sp., schistosomes, and nematodes such as Ascaris sp., to man through the use of sewage sludges as fertilizer is reviewed. The eggs of Ascaris have been found to be the most resistant of these parasites to normal sludge treatment methods. Results of studies on the effectiveness of heat and ionizing radiation treatments reported show that a treatment of 55/sup 0/C for 1 hour or more sufficiently reduces the number of viable Ascaris eggs in seeded sludge systems. An absorbed dose of 300 kilorads radiation is more than adequate for the same purpose. However, before an unequivocal statement can be made about the effectiveness of either of these treatments in reducing viable ova in real systems, certain qualifying factors must be investigated. There are conflicting reports on the radiation sensitivities of Ascaris eggs in different stages of development. Also, irradiation of composted sludge using an electron beam was unsuccessful in rendering all naturally-occurring Ascaris ova non-viable, even at 300 kilorads. The significant differences in radiation and heat sensitivities of Ascaris eggs in compost vs liquid systems points out the need to further investigate the effects of moisture levels on these sensitivities.

Parasites in soil/sludge systems

International Nuclear Information System (INIS)

Brandon, J.R.

1978-03-01

The potential for the transmission of parasites, such as Entamoeba sp., schistosomes, and nematodes such as Ascaris sp., to man through the use of sewage sludges as fertilizer is reviewed. The eggs of Ascaris have been found to be the most resistant of these parasites to normal sludge treatment methods. Results of studies on the effectiveness of heat and ionizing radiation treatments reported show that a treatment of 55 0 C for 1 hour or more sufficiently reduces the number of viable Ascaris eggs in seeded sludge systems. An absorbed dose of 300 kilorads radiation is more than adequate for the same purpose. However, before an unequivocal statement can be made about the effectiveness of either of these treatments in reducing viable ova in real systems, certain qualifying factors must be investigated. There are conflicting reports on the radiation sensitivities of Ascaris eggs in different stages of development. Also, irradiation of composted sludge using an electron beam was unsuccessful in rendering all naturally-occurring Ascaris ova non-viable, even at 300 kilorads. The significant differences in radiation and heat sensitivities of Ascaris eggs in compost vs liquid systems points out the need to further investigate the effects of moisture levels on these sensitivities

Archaeometric studies of Byzantine pottery from Hârşova-Carsium, Romania

Energy Technology Data Exchange (ETDEWEB)

Bugoi, Roxana, E-mail: bugoi@nipne.ro [Horia Hulubei National Institute for Nuclear Physics and Engineering, Mǎgurele 077125 (Romania); Talmaţchi, Cristina, E-mail: ctalmatchi@gmail.com [Museum of National History and Archaeology, Constanţa 900745 (Romania); Haitǎ, Constantin, E-mail: costel_haita@yahoo.com [National Museum of Romania History, Bucharest 030026 (Romania); Ceccato, Daniele, E-mail: daniele.ceccato@lnl.infn.it [Università di Padova, Dipartimento di Fisica e Astronomia “Galileo Galilei”, Padova 35131 (Italy); INFN – LNL, Legnaro 35020 (Italy)

2015-04-01

A set of 36 ceramic shards excavated at Hârşova, Romania, dated to the 11th century A.D., was investigated using Optical Microscopy (OM) and PIXE (Particle Induced X-ray Emission). The study aimed at revealing the raw materials and the manufacturing techniques employed by the potters from the Lower Danube zone during the Byzantine period and to distinguish the local products from the supposedly imported ones. The division of the ceramic shards based on stylistic grounds was refined by the petrographic observations that identified four types of fabrics. Principal Component Analysis (PCA) of the PIXE data singled out two categories of ceramic: one made from kaolinitic clays and another produced from local sedimentary resources, with or without temper addition. Micro-PIXE scans of the interfaces between the green glaze and the underlying ceramic body indicated a high Pb content in the decorative layers. Glazing was made through the application of PbO onto a non-calcareous clay body. The petrographic and compositional data interpreted in correlation with archaeological information led to the characterization of a representative assemblage of ceramic finds from the Byzantine period, subject rarely tackled in the scientific literature.

DNA barcoding of schistosome cercariae reveals a novel sub-lineage within Schistosoma rodhaini from Ngamba Island Chimpanzee Sanctuary, Lake Victoria.

Science.gov (United States)

Standley, C J; Stothard, J R

2012-10-01

While Schistosoma rodhaini is typically considered a parasite of small mammals and is very scantly distributed in the Lake Victoria basin, it is known to hybridize with the more widespread Schistosoma mansoni, the causative agent of intestinal schistosomiasis. As part of broader parasitological and malacological surveys for S. mansoni across Lake Victoria, schistosome cercariae were harvested from a field-caught Biomphalaria choanomphala taken on Ngamba Island Chimpanzee Sanctuary, Uganda. Upon DNA barcoding, these cercariae were found to be a mixture of both S. rodhaini and S. mansoni, with further phylogenetic analysis revealing a hitherto unknown sub-lineage within S. rodhaini. Despite repeated sampling for eggs and miracidia from both chimpanzees and staff on Ngamba Island Sanctuary, detection of S. rodhaini within local definitive hosts awaits additional efforts, which should be mindful of a potential host role of spotted-necked otters.

A novel G protein-coupled receptor of Schistosoma mansoni (SmGPR-3 is activated by dopamine and is widely expressed in the nervous system.

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Fouad El-Shehabi

Full Text Available Schistosomes have a well developed nervous system that coordinates virtually every activity of the parasite and therefore is considered to be a promising target for chemotherapeutic intervention. Neurotransmitter receptors, in particular those involved in neuromuscular control, are proven drug targets in other helminths but very few of these receptors have been identified in schistosomes and little is known about their roles in the biology of the worm. Here we describe a novel Schistosoma mansoni G protein-coupled receptor (named SmGPR-3 that was cloned, expressed heterologously and shown to be activated by dopamine, a well established neurotransmitter of the schistosome nervous system. SmGPR-3 belongs to a new clade of "orphan" amine-like receptors that exist in schistosomes but not the mammalian host. Further analysis of the recombinant protein showed that SmGPR-3 can also be activated by other catecholamines, including the dopamine metabolite, epinine, and it has an unusual antagonist profile when compared to mammalian receptors. Confocal immunofluorescence experiments using a specific peptide antibody showed that SmGPR-3 is abundantly expressed in the nervous system of schistosomes, particularly in the main nerve cords and the peripheral innervation of the body wall muscles. In addition, we show that dopamine, epinine and other dopaminergic agents have strong effects on the motility of larval schistosomes in culture. Together, the results suggest that SmGPR-3 is an important neuronal receptor and is probably involved in the control of motor activity in schistosomes. We have conducted a first analysis of the structure of SmGPR-3 by means of homology modeling and virtual ligand-docking simulations. This investigation has identified potentially important differences between SmGPR-3 and host dopamine receptors that could be exploited to develop new, parasite-selective anti-schistosomal drugs.

Haematological and biochemical characteristics of the splenic effluent blood in schistosomal patients undergoing splenectomy

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Andy Petroianu

Full Text Available OBJECTIVE: To assess hematological and biochemical features of splenic effluent blood and their influence on the rise of hematological values after splenectomy. METHODS: we studied 20 patients undergoing surgical treatment for schistosomatic portal hypertension. We collected blood samples for CBC, coagulation, bilirubin and albumin in the splenic vein (perioperative and peripheral blood (immediately pre and postoperative periods. RESULTS: the splenic blood showed higher values of red blood cells, hemoglobin, hematocrit, platelet count, total leukocytes, neutrophils, lymphocytes, monocytes, eosinophils and basophils, as well as reduction of laboratory coagulation parameters in relation to peripheral blood collected preoperatively. In the postoperative peripheral blood there was an increase in the overall leukocytes and in their neutrophil component, and decreased levels of basophils, eosinophils and lymphocytes. The other postoperative variables of complete blood count and coagulation tests were not different compared with the splenic blood. The albumin values were lower postoperatively when compared to preoperative and splenic blood. There were higher values of direct bilirubin in the postoperative period when compared with the preoperative and splenic blood. Postoperative indirect bilirubin was lower compared to its value in the splenic blood. CONCLUSION: hematological and biochemical values of splenic effluent blood are higher than those found in peripheral blood in the presence of schistosomal splenomegaly. However, the splenic blood effluent is not sufficient to raise the blood levels found after splenectomy.

Application of environmetric methods to investigate control factors on water quality

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Boyacioglu Hülya

2017-09-01

Full Text Available In the study, environmetric methods were successfully performed a to explore natural and anthropogenic controls on reservoir water quality, b to investigate spatial and temporal differences in quality, and c to determine quality variables discriminating three reservoirs in Izmir, Turkey. Results showed that overall water quality was mainly governed by “natural factors” in the whole region. A parameter that was the most important in contributing to water quality variation for one reservoir was not important for another. Between summer and winter periods, difference in arsenic concentrations were statistically significant in the Tahtalı, Ürkmez and iron concentrations were in the Balçova reservoirs. Observation of high/low levels in two seasons was explained by different processes as for instance, dilution from runoff at times of high flow seeped through soil and entered the river along with the rainwater run-off and adsorption. Three variables “boron, arsenic and sulphate” discriminated quality among Balçova & Tahtalı, Balçova & Ürkmez and two variables “zinc and arsenic” among the Tahtalı & Ürkmez reservoirs. The results illustrated the usefulness of multivariate statistical techniques to fingerprint pollution sources and investigate temporal/spatial variations in water quality.

Four whole-istic aspects of schistosome granuloma biology: fractal arrangement, internal regulation, autopoietic component and closure

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HL Lenzi

2006-10-01

Full Text Available This paper centers on some whole-istic organizational and functional aspects of hepatic Schistosoma mansoni granuloma, which is an extremely complex system. First, it structurally develops a collagenic topology, originated bidirectionally from an inward and outward assembly of growth units. Inward growth appears to be originated from myofibroblasts derived from small portal vessel around intravascular entrapped eggs, while outward growth arises from hepatic stellate cells. The auto-assembly of the growth units defines the three-dimensional scaffold of the schistosome granulomas. The granuloma surface irregularity and its border presented fractal dimension equal to 1.58. Second, it is internally regulated by intricate networks of immuneneuroendocrine stimuli orchestrated by leptin and leptin receptors, substance P and Vasoactive intestinal peptide. Third, it can reach the population of ± 40,000 cells and presents an autopoietic component evidenced by internal proliferation (Ki-67+ Cells, and by expression of c-Kit+ Cells, leptin and leptin receptor (Ob-R, granulocyte-colony stimulating factor (G-CSF-R, and erythropoietin (Epo-R receptors. Fourth, the granulomas cells are intimately connected by pan-cadherins, occludin and connexin-43, building a state of closing (granuloma closure. In conclusion, the granuloma is characterized by transitory stages in such a way that its organized structure emerges as a global property which is greater than the sum of actions of its individual cells and extracellular matrix components.

Altered patterns of gene expression underlying the enhanced immunogenicity of radiation-attenuated schistosomes.

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Gary P Dillon

2008-05-01

Full Text Available Schistosome cercariae only elicit high levels of protective immunity against a challenge infection if they are optimally attenuated by exposure to ionising radiation that truncates their migration in the lungs. However, the underlying molecular mechanisms responsible for the altered phenotype of the irradiated parasite that primes for protection have yet to be identified.We have used a custom microarray comprising probes derived from lung-stage parasites to compare patterns of gene expression in schistosomula derived from normal and irradiated cercariae. These were transformed in vitro and cultured for four, seven, and ten days to correspond in development to the priming parasites, before RNA extraction. At these late times after the radiation insult, transcript suppression was the principal feature of the irradiated larvae. Individual gene analysis revealed that only seven were significantly down-regulated in the irradiated versus normal larvae at the three time-points; notably, four of the protein products are present in the tegument or associated with its membranes, perhaps indicating a perturbed function. Grouping of transcripts using Gene Ontology (GO and subsequent Gene Set Enrichment Analysis (GSEA proved more informative in teasing out subtle differences. Deficiencies in signalling pathways involving G-protein-coupled receptors suggest the parasite is less able to sense its environment. Reduction of cytoskeleton transcripts could indicate compromised structure which, coupled with a paucity of neuroreceptor transcripts, may mean the parasite is also unable to respond correctly to external stimuli.The transcriptional differences observed are concordant with the known extended transit of attenuated parasites through skin-draining lymph nodes and the lungs: prolonged priming of the immune system by the parasite, rather than over-expression of novel antigens, could thus explain the efficacy of the irradiated vaccine.

Combining Radiotherapy and Immunotherapy to Target Survivin in Prostate Cancer

Science.gov (United States)

2009-01-01

EL4 ). All mice apart from the 20Gy-irradiated...4x 4G y 5G y 10 G y 20 G y control EL4 EG7.OVA IF N γ sp ot s/ 1 x1 05 s pl en oc yt es OVA-specific immune responses IFNγ -ELISPOT 0 0.1 0.2 0.3...300 350 ELISPOT 1-4-09 control EL4 EG7.OVA OVA peptide IF Nγ s po ts / 1x 10 5 sp le no cy te s no treatment 4x4Gy MIS416

Expression profile of the Schistosoma japonicum degradome reveals differential protease expression patterns and potential anti-schistosomal intervention targets.

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Shuai Liu

2014-10-01

Full Text Available Blood fluke proteases play pivotal roles in the processes of invasion, nutrition acquisition, immune evasion, and other host-parasite interactions. Hundreds of genes encoding putative proteases have been identified in the recently published schistosome genomes. However, the expression profiles of these proteases in Schistosoma species have not yet been systematically analyzed. We retrieved and culled the redundant protease sequences of Schistosoma japonicum, Schistosoma mansoni, Echinococcus multilocularis, and Clonorchis sinensis from public databases utilizing bioinformatic approaches. The degradomes of the four parasitic organisms and Homo sapiens were then comparatively analyzed. A total of 262 S. japonicum protease sequences were obtained and the expression profiles generated using whole-genome microarray. Four main clusters of protease genes with different expression patterns were identified: proteases up-regulated in hepatic schistosomula and adult worms, egg-specific or predominantly expressed proteases, cercaria-specific or predominantly expressed proteases, and constantly expressed proteases. A subset of protease genes with different expression patterns were further validated using real-time quantitative PCR. The present study represents the most comprehensive analysis of a degradome in Schistosoma species to date. These results provide a firm foundation for future research on the specific function(s of individual proteases and may help to refine anti-proteolytic strategies in blood flukes.

Effect of Maternal Intake of Organically or Conventionally Produced Feed on Oral Tolerance Development in Offspring Rats

DEFF Research Database (Denmark)

Melballe Jensen, Maja; Halekoh, Ulrich; Stokes, Christopher

2013-01-01

(organic or conventional) or a chow. Second-generation rats were exposed to ovalbumin (OVA) via their mother’s milk and subsequently challenged with OVA after weaning onto the chow diet. In the chow diet group feeding the dams OVA resulted in suppression of the pups’ anti-OVA antibody response to the OVA...... challenge (total OVA-specific IgG was 197 for the OVA-treated chow diet group and 823 for the control chow diet group (arbitrary ELISA units)). In contrast, OVA exposure of the dams from the plant-based dietary groups did not result in a similar suppression. Cultivation system had no effect...... on the immunological biomarkers, except for a higher spleen prostaglandin E2 (PGE2) concentration in pups originating from dams fed the conventional plant-based diet (223 ng/L) than from those fed the organic plant-based diet (189 ng/L)....

Schistosoma haematobium treatment in 1-5 year old children: safety and efficacy of the antihelminthic drug praziquantel.

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Francisca Mutapi

2011-05-01

Full Text Available Morbidity due to schistosomiasis is currently controlled by treatment of schistosome infected people with the antihelminthic drug praziquantel (PZQ. Children aged up to 5 years are currently excluded from schistosome control programmes largely due to the lack of PZQ safety data in this age group. This study investigated the safety and efficacy of PZQ treatment in such children.Zimbabwean children aged 1-5 years (n = 104 were treated with PZQ tablets and side effects were assessed by questionnaire administered to their caregivers within 24 hours of taking PZQ. Treatment efficacy was determined 6 weeks after PZQ administration through schistosome egg counts in urine. The change in infection levels in the children 1-5 years old (n = 100 was compared to that in 6-10 year old children (n = 435.Pre-treatment S. haematobium infection intensity in 1-5 year olds was 14.6 eggs/10 ml urine and prevalence was 21%. Of the 104 children, 3.8% reported side effects within 24 hours of taking PZQ treatment. These were stomach ache, loss of appetite, lethargy and inflammation of the face and body. PZQ treatment significantly reduced schistosome infection levels in 1-5 year olds with an egg reduction rate (ERR of 99% and cure rate (CR of 92%. This was comparable to the efficacy of praziquantel in 6-10 year olds where ERR was 96% and CR was 67%. INTERPRETATION/SIGNIFICANCE: PZQ treatment is as safe and efficacious in children aged 1-5 years as it is in older children aged 6-10 years in whom PZQ is the drug of choice for control of schistosome infections.

Obesity increases airway hyperresponsiveness via the TNF-α pathway and treating obesity induces recovery.

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Joo Young Kim

Full Text Available Obesity is a known risk factor for allergic asthma. It has been recognized as a key player in the pathogenesis of several inflammatory disorders via activation of macrophages, which is also vital to the development of allergic asthma. We investigated the mechanism of obesity-related asthma and whether treating obesity through exercise or diet ameliorates the severity of asthma in the obesity-related asthma model. We generated diet-induced obesity (DIO in C57BL/6 mice by high-fat-feeding and ovalbumin-induced asthma (lean-OVA or DIO-OVA. The DIO-OVA mice were then treated with tumor necrosis factor (TNF-α neutralizing antibody as a TNF-α blockade or a Cl2MDP-containing liposome to induce an alveolar macrophage deficiency. To treat obesity, the DIO-OVA mice were under dietary restrictions or exercised. The pathophysiological and immunological responses were analyzed. Airway hyperresponsiveness (AHR, serum IgE and TNF-α levels in the lung tissue increased in the DIO-OVA mice compared to the lean-OVA mice. Both the TNF-α blockade and depletion of alveolar macrophages in the DIO-OVA mice decreased AHR compared to the DIO-OVA mice. Treating obesity by exercise or through dietary means also reduced pulmonary TNF-α levels and AHR in the DIO-OVA mice. These results suggest that restoring normal body weight is an appropriate strategy for reducing TNF-α levels, and controlling inflammation may help improve asthma severity and control in obesity-related asthma.

Changes of the antigenic and allergenic properties of a hen's egg albumin in a cake with gamma-irradiated egg white

International Nuclear Information System (INIS)

Lee, J.-W.; Seo, J.-H.; Kim, J.-H.; Lee, S.-Y.; Kim, K.-S.; Byun, M.-W.

2005-01-01

Changes of the antigenicity and allergenicity of a hen's egg albumin (ovalbumin, OVA) in white layer cakes containing egg white gamma-irradiated with 10 or 20 kGy were monitored by an enzyme-linked immunosorbent assay (ELISA), individually formatted with mouse anti-OVA IgG (mouse IgG) and with egg allergic patients' IgE. Mouse IgG recognized OVA in the cakes with irradiated egg white better than that in the control with a non-irradiated one. Whereas, the detected concentrations of intact OVA in the control significantly decreased in the treatments, when determined by IgE-based ELISA. The results appeared to indicate that the antigenicity of the OVA increased, but that the allergenicity was decreased by irradiation and processing. Egg white irradiated for reducing the egg allergy could be used for producing a safer cake from the egg allergy

Schistosome-induced cholangiocyte proliferation and osteopontin secretion correlate with fibrosis and portal hypertension in human and murine schistosomiasis mansoni.

Science.gov (United States)

Pereira, Thiago A; Syn, Wing-Kin; Machado, Mariana V; Vidigal, Paula V; Resende, Vivian; Voieta, Izabela; Xie, Guanhua; Otoni, Alba; Souza, Márcia M; Santos, Elisângela T; Chan, Isaac S; Trindade, Guilherme V M; Choi, Steve S; Witek, Rafal P; Pereira, Fausto E; Secor, William E; Andrade, Zilton A; Lambertucci, José Roberto; Diehl, Anna Mae

2015-11-01

Schistosomiasis is a major cause of portal hypertension worldwide. It associates with portal fibrosis that develops during chronic infection. The mechanisms by which the pathogen evokes these host responses remain unclear. We evaluated the hypothesis that schistosome eggs release factors that directly stimulate liver cells to produce osteopontin (OPN), a pro-fibrogenic protein that stimulates hepatic stellate cells to become myofibroblasts. We also investigated the utility of OPN as a biomarker of fibrosis and/or severity of portal hypertension. Cultured cholangiocytes, Kupffer cells and hepatic stellate cells were treated with soluble egg antigen (SEA); OPN production was quantified by quantitative reverse transcriptase polymerase chain reaction (qRTPCR) and ELISA; cell proliferation was assessed by BrdU (5-bromo-2'-deoxyuridine). Mice were infected with Schistosoma mansoni for 6 or 16 weeks to cause early or advanced fibrosis. Liver OPN was evaluated by qRTPCR and immunohistochemistry (IHC) and correlated with liver fibrosis and serum OPN. Livers from patients with schistosomiasis mansoni (early fibrosis n=15; advanced fibrosis n=72) or healthy adults (n=22) were immunostained for OPN and fibrosis markers. Results were correlated with plasma OPN levels and splenic vein pressures. SEA-induced cholangiocyte proliferation and OPN secretion (Pportal hypertension severity. © 2015 Authors; published by Portland Press Limited.

Maternal and paternal genomes function independently in mouse ova in establishing expression of the imprinted genes Snrpn and Igf2r: no evidence for allelic trans-sensing and counting mechanisms.

OpenAIRE

Szabó, P E; Mann, J R

1996-01-01

It has often been suggested that the parental-specific expression of mammalian imprinted genes might be dependent on maternal-paternal intergenomic or interallelic interactions. Using quantitative allele-specific RT-PCR single nucleotide primer extension assays developed for two imprinted genes, Snrpn and Igf2r, we demonstrate: (i) No role for maternal-paternal allelic interactions: the modes of parental-specific expression of Snrpn and Igf2r in normal ova were unchanged in gynogenetic and an...

Changes of the antigenic and allergenic properties of a hen's egg albumin in a cake with gamma-irradiated egg white

Energy Technology Data Exchange (ETDEWEB)

Lee, J.-W.; Seo, J.-H.; Kim, J.-H.; Lee, S.-Y.; Kim, K.-S.; Byun, M.-W. E-mail: mwbyun@nanum.kaeri.re.kr

2005-04-01

Changes of the antigenicity and allergenicity of a hen's egg albumin (ovalbumin, OVA) in white layer cakes containing egg white gamma-irradiated with 10 or 20 kGy were monitored by an enzyme-linked immunosorbent assay (ELISA), individually formatted with mouse anti-OVA IgG (mouse IgG) and with egg allergic patients' IgE. Mouse IgG recognized OVA in the cakes with irradiated egg white better than that in the control with a non-irradiated one. Whereas, the detected concentrations of intact OVA in the control significantly decreased in the treatments, when determined by IgE-based ELISA. The results appeared to indicate that the antigenicity of the OVA increased, but that the allergenicity was decreased by irradiation and processing. Egg white irradiated for reducing the egg allergy could be used for producing a safer cake from the egg allergy.

Schistosomiasis research in the dongting lake region and its impact on local and national treatment and control in China.

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Donald P McManus

2011-08-01

Full Text Available Schistosomiasis is a chronic and debilitating parasitic disease that has often been neglected because it is a disease of poverty, affecting poor rural communities in the developing world. This is not the case in the People's Republic of China (PRC, where the disease, caused by Schistosoma japonicum, has long captured the attention of the Chinese authorities who have, over the past 50-60 years, undertaken remarkably successful control programs that have substantially reduced the schistosomiasis disease burden. The Dongting Lake region in Hunan province is one of the major schistosome-endemic areas in the PRC due to its vast marshland habitats for the Oncomelania snail intermediate hosts of S. japonicum. Along with social, demographic, and other environmental factors, the recent completion and closure of the Three Gorges dam will most likely increase the range of these snail habitats, with the potential for re-emergence of schistosomiasis and increased transmission in Hunan and other schistosome-endemic provinces being a particular concern. In this paper, we review the history and the current status of schistosomiasis control in the Dongting Lake region. We explore the epidemiological factors contributing to S. japonicum transmission there, and summarise some of the key research findings from studies undertaken on schistosomiasis in Hunan province over the past 10 years. The impact of this research on current and future approaches for sustainable integrated control of schistosomiasis in this and other endemic areas in the PRC is emphasised.

Effect of electron beam irradiation on bacterial and Ascaris ova loads and volatile organic compounds in municipal sewage sludge

International Nuclear Information System (INIS)

Engohang-Ndong, Jean; Uribe, R.M.; Gregory, Roger; Gangoda, Mahinda; Nickelsen, Mike G.; Loar, Philip

2015-01-01

Wastewater treatment plants produce large amounts of biosolids that can be utilized for land applications. However, prior to their use, these biosolids must be treated to eliminate risks of infections and to reduce upsetting odors. In this study, microbiological and chemical analyzes were performed before and after treatment of sewage sludge with 3 MeV of an electron beam accelerator in a pilot processing plant. Thus, we determined that dose 4.5 kGy was required to reduce fecal coliform counts to safe levels for land applications of sludge while, 14.5 kGy was necessary to decrease Ascaris ova counts to safe levels. Furthermore, at low doses, electron beam irradiation showed little effect on the concentrations of volatile organic compounds, while some increase were recorded at high doses. The concentration of dimethyl sulfide was reduced by 50–70% at irradiation doses of 25.7 kGy and 30.7 kGy respectively. By contrast, electron beam irradiation increased dimethyl disulfide concentrations. We also showed that electron beam treatment was less energy-consuming with shorter processing times than conventional techniques used to decontaminate sludge. Hence opening new avenues for large urban agglomerations to save money and time when treating biosolids for land application. - Highlights: • Use of electron beam irradiation for the treatment of municipal sewage sludge. • Irradiation at 4.5 kGy is required to eliminate risks of bacterial infection. • Irradiation at 14.5 kGy is required to eliminate risks of helminth infection. • Electron beam technology is not effective for controlling volatile organic compounds. • Electron beam treatment of sludge is less expensive than traditional techniques

Blockade of PD-1 Signaling Enhances Th2 Cell Responses and Aggravates Liver Immunopathology in Mice with Schistosomiasis japonica.

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Sha Zhou

2016-10-01

Full Text Available More than 220 million people worldwide are chronically infected with schistosomes, causing severe disease or even death. The major pathological damage occurring in schistosomiasis is attributable to the granulomatous inflammatory response and liver fibrosis induced by schistosome eggs. The inflammatory response is tightly controlled and parallels immunosuppressive regulation, constantly maintaining immune homeostasis and limiting excessive immunopathologic damage in important host organs. It is well known that the activation of programmed death 1 (PD-1 signaling causes a significant suppression of T cell function. However, the roles of PD-1 signaling in modulating CD4+ T cell responses and immunopathology during schistosome infection, have yet to be defined.Here, we show that PD-1 is upregulated in CD4+ T cells in Schistosoma japonicum (S. japonicum-infected patients. We also show the upregulation of PD-1 expression in CD4+ T cells in the spleens, mesenteric lymph nodes, and livers of mice with S. japonicum infection. Finally, we found that the blockade of PD-1 signaling enhanced CD4+ T helper 2 (Th2 cell responses and led to more severe liver immunopathology in mice with S. japonicum infection, without a reduction of egg production or deposition in the host liver.Overall, our study suggests that PD-1 signaling is specifically induced to control Th2-associated inflammatory responses during schistosome infection and is beneficial to the development of PD-1-based control of liver immunopathology.

Integrated control programmes for schistosomiasis and other helminth infections in P.R. China.

Science.gov (United States)

Xu, Jing; Xu, Jun-Fang; Li, Shi-Zhu; Zhang, Li-Juan; Wang, Qiang; Zhu, Hui-Hui; Zhou, Xiao-Nong

2015-01-01

The prevalence of human schistosomiasis and soil-transmitted helminthiasis (STH) has decreased significantly in the People's Republic of China (P.R. China), particularly after 2005 when the national control programmes were reinforced by forming of integrated control strategies. Furthermore, social-economic development also contributed to the decrease of schistosome and soil-transmitted helminth infections. The prevalence of the zoonotic helminthiasis, including clonorchiasis and echinococcosis, on the other hand, is either underestimated or has in fact increased due to changes in social and environmental factors. In comparison with the control strategies in force and their effects on those four kinds of helminthiasis, the challenges and control priorities for the potential transfer from control to elimination of each disease is reviewed, to provide evidence for policy-makers to act upon. Copyright © 2013 Elsevier B.V. All rights reserved.

Effect of liposomal formulations and immunostimulating peptidoglycan monomer (PGM) on the immune reaction to ovalbumin in mice.

Science.gov (United States)

Habjanec, Lidija; Frkanec, Ruza; Halassy, Beata; Tomasić, Jelka

2006-01-01

The adjuvant activity of liposomes and immunostimulating peptidoglycan monomer (PGM) in different formulations has been studied in mice model using ovalbumin (OVA) as an antigen. PGM is a natural compound of bacterial origin with well-defined chemical structure: GlcNAc-MurNAc-L-Ala-D-isoGln-mesoDpm(epsilonNH2)-D-Ala-D-Ala. It is a non-toxic, non-pyrogenic, and water-soluble immunostimulator. The aim of this study was to investigate the influence of different liposomal formulations of OVA, with or without PGM, on the production of total IgG, as well as of IgG1 and IgG2a subclasses of OVA-specific antibodies (as indicators of Th2 and Th1 type of immune response, respectively). CBA mice were immunized s.c. with OVA mixed with liposomes, OVA with PGM mixed with liposomes, OVA encapsulated into liposomes and OVA with PGM encapsulated into liposomes. Control groups were OVA in saline, OVA with PGM in saline, and OVA in CFA/IFA adjuvant formulation. The entrapment efficacy of OVA was monitored by HPLC method. The adjuvant activity of the mixture of OVA and empty liposomes, the mixture of OVA, PGM, and liposomes and PGM encapsulated with OVA into liposomes on production of total anti-OVA IgG was demonstrated. The mixture of PGM and liposomes exhibited additive immunostimulating effect on the production of antigen-specific IgGs. The analysis of IgG subclasses revealed that encapsulation of OVA into liposomes favors the stimulation of IgG2a antibodies, indicating the switch toward the Th1 type of immune response. When encapsulated into liposomes or mixed with liposomes, PGM induced a switch from Th1 to Th2 type of immune response. It could be concluded that appropriate formulations of antigen, PGM, and liposomes differently affect the humoral immune response and direct the switch in the type of immune response (Th1/Th2).

[Study on interventions based on urban - rural integration system construction to consolidate achievements of schistosomiasis control in hilly schistosomiasis endemic areas].

Science.gov (United States)

Rong-Zhi, Li; Yang, Liu; Hui, Zhang; Yi, Zhang; Bo, Zhong; Jian-Jun, Wu; Chun-Xia, Yang

2017-09-28

To explore the effectiveness of comprehensive schistosomiasis control interventions based on urban-rural integration system construction to carry out the schistosomiasis control in hilly schistosomiasis endemic areas, so as to offer a new mode to consolidate the achievements of schistosomiasis control in the new situation. Shouan Town and Changqiu Township in Pujiang County in hilly schistosomiasis endemic regions were selected as demonstration areas. The comprehensive schistosomiasis control interventions based on urban-rural integration system construction were implemented, including the land consolidation, centralized residence and so on. The effectiveness the interventions was evaluated. In Shouan Town and Changqiu Township, the transformed environments with Oncomelania hupensis snail habitats were 1 330.61 hm 2 and 1 456.84 hm 2 , the areas with snails decreased from 94.31 hm 2 and 83.00 hm 2 in 2000 to both 0 in 2015, the positive rates of serological tests for schistosomiasis decreased from 11.8% and 7.53% in 2000 to 1.01% and 1.86% in 2015, and the positive rates of parasitological tests decreased from 0.18% and 0.15% in 2000 to both 0 in 2015 respectively. The numbers of cattle decreased from 358 and 368 in 2000 to 4 and 6 in 2015 respectively. In 2000, the schistosome infection rates of cattle were 3.63% and 6.51% in Shouan Town and Changqiu Township respectively, and from 2004, no infected cattle were found. The comprehensive schistosomiasis control interventions based on urban-rural integration system construction can decrease the schistosome infection rate and area with snails effectively, providing a new mode for schistosomiasis elimination.

Comparative Analysis of Proteome-Wide Lysine Acetylation in Juvenile and Adult Schistosoma japonicum

Directory of Open Access Journals (Sweden)

Qing Li

2017-11-01

Full Text Available Schistosomiasis is a devastating parasitic disease caused by tremotodes of the genus Schistosoma. Eggs produced by sexually mature schistosomes are the causative agents of for pathogenesis and transmission. Elucidating the molecular mechanism of schistosome development and sexual maturation would facilitate the prevention and control of schistosomiasis. Acetylation of lysine is a dynamic and reversible post-translational modification playing keys role in many biological processes including development in both eukaryotes and prokaryotes. To investigate the impacts of lysine acetylation on Schistosoma japonicum (S. japonicum development and sexual maturation, we used immunoaffinity-based acetyllysine peptide enrichment combined with mass spectrometry (MS, to perform the first comparative analysis of proteome-wide lysine acetylation in both female and male, juvenile (18 days post infection, 18 dpi and adult (28 dpi schistosome samples. In total, we identified 874 unique acetylated sites in 494 acetylated proteins. The four samples shared 47 acetylated sites and 46 proteins. More acetylated sites and proteins shared by both females and males were identified in 28 dpi adults (189 and 143, respectively than in 18 dpi schistosomula (76 and 59, respectively. More stage-unique acetylated sites and proteins were also identified in 28 dpi adults (494 and 210, respectively than in 18 dpi schistosomula (73 and 44, respectively. Functional annotation showed that in different developmental stages and genders, a number of proteins involving in muscle movement, glycometabolism, lipid metabolism, energy metabolism, environmental stress resistance, antioxidation, etc., displayed distinct acetylation profiles, which was in accordance with the changes of their biological functions during schistosome development, suggesting that lysine acetylation modification exerted important regulatory roles in schistosome development. Taken together, our data provided the first

Use of recombinant calreticulin and cercarial transformation fluid (CTF) in the serodiagnosis of Schistosoma mansoni.

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El Aswad, Bahaa El Deen Wade; Doenhoff, Michael J; El Hadidi, Abeer Shawky; Schwaeble, Wilhelm J; Lynch, Nicholas J

2011-03-01

Schistosomiasis is traditionally diagnosed by microscopic detection of ova in stool samples, but this method is labour intensive and its sensitivity is limited by low and variable egg secretion in many patients. An alternative is an ELISA using Schistosoma mansoni soluble egg antigen (SEA) to detect anti-schistosome antibody in patient samples. SEA is a good diagnostic marker in non-endemic regions but is of limited value in endemic regions, mainly because of its high cost and limited specificity. Here we assess seven novel antigens for the detection of S. mansoni antibody in an endemic region (the Northern Nile Delta). Using recombinant S. mansoni calreticulin (CRT) and fragments thereof, anti-CRT antibodies were detected in the majority of 97 patients sera. The diagnostic value of some of these antigens was, however, limited by the presence of cross-reacting antibody in the healthy controls, even those recruited in non-endemic areas. Cercarial transformation fluid (CTF), a supernatant that contains soluble material released by the cercariae upon transformation to the schistosomula, is cheaper and easier to produce than SEA. An ELISA using CTF as the detection antigen had a sensitivity of 89.7% and an estimated specificity of 100% when used in non-endemic regions, matching the performance of the established SEA ELISA. CTF was substantially more specific than SEA for diagnosis in the endemic region, and less susceptible than SEA to cross-reacting antibody in the sera of controls with other protozoan and metazoan infections. Copyright © 2010 Elsevier GmbH. All rights reserved.

Influence of a cocoa-enriched diet on specific immune response in ovalbumin-sensitized rats.

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Pérez-Berezo, Teresa; Ramiro-Puig, Emma; Pérez-Cano, Francisco J; Castellote, Cristina; Permanyer, Joan; Franch, Angels; Castell, Margarida

2009-03-01

Previous studies in young rats have reported the impact of 3 weeks of high cocoa intake on healthy immune status. The present article describes the effects of a longer-term cocoa-enriched diet (9 weeks) on the specific immune response to ovalbumin (OVA) in adult Wistar rats. At 4 weeks after immunization, control rats produced anti-OVA antibodies, which, according their amount and isotype, were arranged as follows: IgG1 > IgG2a > IgM > IgG2b > IgG2c. Both cocoa diets studied (4% and 10%) down-modulated OVA-specific antibody levels of IgG1 (main subclass associated with the Th2 immune response in rats), IgG2a, IgG2c and IgM isotypes. Conversely, cocoa-fed rats presented equal or higher levels of anti-OVA IgG2b antibodies (subclass linked to the Th1 response). Spleen and lymph node cells from OVA-immunized control and cocoa-fed animals proliferated similarly under OVA stimulation. However, spleen cells from cocoa-fed animals showed decreased interleukin-4 secretion (main Th2 cytokine), and lymph node cells from the same rats displayed higher interferon-gamma secretion (main Th1 cytokine). These changes were accompanied by a reduction in the number of anti-OVA IgG-secreting cells in spleen. In conclusion, cocoa diets induced attenuation of antibody synthesis that may be attributable to specific down-regulation of the Th2 immune response.

An artemisinin derivative of praziquantel as an orally active antischistosomal agent.

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Lanlan Dong

Full Text Available Schistosomiasis is a major health problem in tropical and sub-tropical areas caused by species of trematode belonging to the genus Schistosoma. The treatment and control of this disease has been relying on the use of a single drug praziquantel. However, the drug resistance concern urged the development of new drugs against schistosoma. Here, we report our systematic biological evaluation of DW-3-15, a new lead compound developed based on our conjugation design rationale as an effective anti-schistosomal agent.The antischistosomal activity of DW-3-15 was systematically evaluated in S. japonicum infected mouse model for its stage-sensitivity and dose response. The results revealed that DW-3-15 exhibited 60-85% worm reduction rate against different development stage of worm. Scanning electron microscopy (SEM observation indicated that DW-3-15 may damage to the tegument of male schistosomes.Our results demonstrated that DW-3-15 showed potent anti-schistosomal activities in vivo. The results strongly support our conjugation design strategy of artemisinin analogs and further development of DW-3-15 as a new lead compound as anti-schistosomal agent.

Effects of gasoline engine emissions on preexisting allergic airway responses in mice.

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Day, Kimberly C; Reed, Matthew D; McDonald, Jacob D; Seilkop, Steven K; Barrett, Edward G

2008-10-01

Gasoline-powered vehicle emissions contribute significantly to ambient air pollution. We hypothesized that exposure to gasoline engine emissions (GEE) may exacerbate preexisting allergic airway responses. Male BALB/c mice were sensitized by injection with ovalbumin (OVA) and then received a 10-min aerosolized OVA challenge. Parallel groups were sham-sensitized with saline. Mice were exposed 6 h/day to air (control, C) or GEE containing particulate matter (PM) at low (L), medium (M), or high (H) concentrations, or to the H level with PM removed by filtration (high-filtered, HF). Immediately after GEE exposure mice received another 10-min aerosol OVA challenge (pre-OVA protocol). In a second (post-OVA) protocol, mice were similarly sensitized but only challenged to OVA before air or GEE exposure. Measurements of airway hyperresponsiveness (AHR), bronchoalveolar lavage (BAL), and blood collection were performed approximately 24 h after the last exposure. In both protocols, M, H, and HF GEE exposure significantly decreased BAL neutrophils from nonsensitized mice but had no significant effect on BAL cells from OVA-sensitized mice. In the pre-OVA protocol, GEE exposure increased OVA-specific IgG(1) but had no effect on BAL interleukin (IL)-2, IL-4, IL-13, or interferon (IFN)-gamma in OVA-sensitized mice. Nonsensitized GEE-exposed mice had increased OVA-specific IgG(2a), IgE, and IL-2, but decreased total IgE. In the post-OVA protocol, GEE exposure reduced BAL IL-4, IL-5, and IFN-gamma in nonsensitized mice but had no effect on sensitized mice. These results suggest acute exposure to the gas-vapor phase of GEE suppressed inflammatory cells and cytokines from nonsensitized mice but did not substantially exacerbate allergic responses.

The identification of plant lectins with mucosal adjuvant activity

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Lavelle, E C; Grant, G; Pusztai, A; Pfüller, U; O'hagan, D T

2001-01-01

To date, the most potent mucosal vaccine adjuvants to be identified have been bacterial toxins. The present data demonstrate that the type 2 ribosome-inactivating protein (type 2 RIP), mistletoe lectin I (ML-I) is a strong mucosal adjuvant of plant origin. A number of plant lectins were investigated as intranasal (i.n.) coadjuvants for a bystander protein, ovalbumin (OVA). As a positive control, a potent mucosal adjuvant, cholera toxin (CT), was used. Co-administration of ML-I or CT with OVA stimulated high titres of OVA-specific serum immunoglobulin G (IgG) in addition to OVA-specific IgA in mucosal secretions. CT and ML-I were also strongly immunogenic, inducing high titres of specific serum IgG and specific IgA at mucosal sites. None of the other plant lectins investigated significantly boosted the response to co-administered OVA. Immunization with phytohaemagglutinin (PHA) plus OVA elicited a lectin-specific response but did not stimulate an enhanced response to OVA compared with the antigen alone. Intranasal delivery of tomato lectin (LEA) elicited a strong lectin-specific systemic and mucosal antibody response but only weakly potentiated the response to co-delivered OVA. In contrast, administration of wheatgerm agglutinin (WGA) or Ulex europaeus lectin 1 (UEA-I) with OVA stimulated a serum IgG response to OVA while the lectin-specific responses (particularly for WGA) were relatively low. Thus, there was not a direct correlation between immunogenicity and adjuvanticity although the strongest adjuvants (CT, ML-I) were also highly immunogenic. PMID:11168640

Adjuvant activity of peptidoglycan monomer and its metabolic products.

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Halassy, Beata; Krstanović, Marina; Frkanec, Ruza; Tomasić, Jelka

2003-02-14

Peptidoglycan monomer (PGM) is a natural compound of bacterial origin. It is a non-toxic, non-pyrogenic, water-soluble immunostimulator potentiating humoral immune response to ovalbumin (OVA) in mice. It is fast degraded and its metabolic products-the pentapeptide (PP) and the disaccharide (DS)-are excreted from the mammalian organism upon parenteral administration. The present study investigates: (a). whether PGM could influence the long-living memory generation; (b). whether metabolic products retain adjuvant properties of the parent compound and contribute to its adjuvanticity. We report now that mice immunised twice with OVA+PGM had significantly higher anti-OVA IgG levels upon challenge with antigen alone 6 months later in comparison to control group immunised with OVA only. PP and DS were prepared enzymatically in vitro as apyrogenic and chemically pure compounds. When mice were immunised with OVA plus PP and DS, respectively, the level of anti-OVA IgGs in sera was not higher than in mice immunised with OVA alone, while PGM raised the level of specific antibodies. Results implicate that the adjuvant active molecule, capable of enhancing long-living memory generation, is PGM itself, and none of its metabolic products.

[Effect of ecological civilized homestead construction on schistosomiasis control].

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Tang, Meng; Jia, Tie-Wu; Wu, Zi-Song; Mao, Ping; Chen, Lin; Li, Han-Gang; Zhong, Bo; Qiu, Dong-Chuan; Yao, Qin; Hu, You-Ping

2012-02-01

To evaluate the effect of Ecological Civilized Homestead Construction on schistosomiasis control. The data of ecological civilized homestead construction and schistosomiasis control were collected and analyzed in Meiwan Village, Shuangqiao Town, Danling County, Sichuan Province from 2004 to 2010. Ecological Civilized Homestead Construction was carried out from 2004 to 2010. Totally 454 bio-gas pools were built. All the farmers used well water. The popularized rates of the household bio-gas pool, sanitary toilet, sewage treatment pool reached 100%. The number of cattle was 4, which decreased by 91.30% compared with that in 2004, and all the cattle were fed in captivity. The schistosome infection rates of populations were 0.26% and 0.30% in 2005 and 2008, respectively, and nobody was infected in other years. The infection rate of cattle was 0 from 2004 to 2010. The awareness rate of knowledge about schistosomiasis control achieved 100% in the population over 6 years old. Most of the farmers could use certain protective measures while they were farming. The effect of ecological civilized homestead construction on schistosomiasis control is remarkable.

Murine eosinophils labeled with indium-111 oxine: localization to delayed hypersensitivity reactions against a schistosomal antigen and to lymphokine in vivo

International Nuclear Information System (INIS)

Rand, T.H.; Clanton, J.A.; Runge, V.; English, D.; Colley, D.G.

1983-01-01

We have evaluated a method for quantitation of eosinophil migration to stimuli in vivo. Upon transfusion into normal syngeneic mice, 111In-labeled eosinophils had an intravascular half-life of 9.5 hr and distributed predominantly into spleen, bone marrow, and liver. In either Schistosoma mansoni-infected mice or recipients of lymphoid cells from infected mice, intradermal (ear pinna) injection of the schistosomal egg antigenic preparation (SEA) elicited time-dependent accumulation of 111In-labeled eosinophils detectable by either gamma scintillation counting of tissue samples or by nuclear medicine external imaging. Intradermal administration of a lymphokine fraction (containing eosinophil stimulation promoter activity) similarly caused accumulation of 111In-labeled eosinophils. Both reactions depended on the concentration of stimulus (SEA or lymphokine). 111In-labeled neutrophils or macrophages or 125I-albumin did not preferentially accumulate at the reactions examined to the extent found with 111In-labeled eosinophils, indicating that localization of label depends on an active process and is due to eosinophils rather than a contaminating cell type. The method was used to estimate how long eosinotactic lymphokine remained at dermal sites: 60% of initial activity was present 12 hr after injection. The model is discussed with regard to the role of lymphokines in hypersensitivity reactions with eosinophil involvement, such as the granulomatous response to S. mansoni eggs

Immunoadjuvant activity, toxicity assays, and determination by UPLC/Q-TOF-MS of triterpenic saponins from Chenopodium quinoa seeds.

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Verza, Simone G; Silveira, Fernando; Cibulski, Samuel; Kaiser, Samuel; Ferreira, Fernando; Gosmann, Grace; Roehe, Paulo M; Ortega, George G

2012-03-28

The adjuvant activity of Chenopodium quinoa (quinoa) saponins on the humoral and cellular immune responses of mice subcutaneously immunized with ovalbumin (OVA) was evaluated. Two quinoa saponin fractions were obtained, FQ70 and FQ90, and 10 saponins were determined by UPLC/Q-TOF-MS. Mice were immunized subcutaneously with OVA alone or adjuvanted with Quil A (adjuvant control), FQ70, or FQ90. FQ70 and FQ90 significantly enhanced the amount of anti-OVA-specific antibodies in serum (IgG, IgG1, and IgG2b) in immunized mice. The adjuvant effect of FQ70 was significantly greater than that of FQ90. However, delayed type hypersensitivity responses were higher in mice immunized with OVA adjuvanted with FQ90 than mice treated with FQ70. Concanavalin A (Con A)-, lipopolysaccharide-, and OVA-stimulated splenocyte proliferation were measured, and FQ90 significantly enhanced the Con A-induced splenocyte proliferation. The results suggested that the two quinoa saponin fractions enhanced significantly the production of humoral and cellular immune responses to OVA in mice.

Effect of wide spectrum anti-helminthic drugs upon Schistosoma mansoni experimentally infected mice

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PANCERA Christiane Finardi

1997-01-01

Full Text Available Mebendazole, albendazole, levamisole and thiabendazole are well known as active drugs against several nematode species, and against cestodes as well, when the first two drugs are considered. None of the drugs have proven activity, however, against trematodes. We tested the effect of these drugs on the fecal shedding of schistosome eggs and the recovering of adult schistosomes, after portal perfusion in Schistosoma mansoni experimentally infected mice. Balb/c mice infected with 80 S. mansoni cercariae were divided into three groups, each in turn subdivided into four other groups, for each tested drug. The first group was treated with each one of the studied drugs 25 days after S. mansoni infection; the second group was submitted to treatment with each one of the drugs 60 days after infection. Finally, the third group, considered as control, received no treatment. No effect upon fecal shedding of S. mansoni eggs and recovering of schistosomes after portal perfusion was observed when mice were treated with either mebendazole or albendazole. Mice treated with either levamisole or thiabendazole, on the other hand, showed a significant reduction in the recovering of adult schistosomes after portal perfusion, mainly when both drugs were given during the schistosomula evolution period, i.e., 25 days after cercariae penetration, probably due to unspecific immunomodulation

Composición de ácidos grasos en ovas de trucha arco iris (Oncorhynchus mykiss, Walbaum, 1792

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Rafael Rosado Puccini

2012-06-01

Full Text Available En este artículo se analizan con parámetros de composición 58 puestas de trucha arcoiris obtenidas, manejadas y monitoreadas individualmente en desempeño desde la fertilización hasta finalizar la etapa de reabsorción de vesícula. Además de los valores reproductivos, el contenido de ácidos grasos en las ovas se determinó en fresco, mediante cromatografía de gases. En el perfil medio se destacan los ácidos palmítico (C16, oleico (C18:1n-9 y docosahexaenoico (C22:6n-3 como los más representativos, con casi el 60% del total y, en general, en concentraciones estables entre las hembras. Tanto para cada ácido determinado como para el conjunto de contenidos integrados de las series n-3 y n-6, y los colectivos de saturados (SAF, monoinsaturados (MUFA y poliinsaturados (PUFA, se define un patrón de composición similar al reportado para la especie en otros esquemas de manejo y bajo regímenes nutricionales variables. Se analizó la condición conservativa en la incorporación de ácidos grasos al huevo, y se discutió su utilidad como posibles definitorios de calidad, teniendo como referente la alta variabilidad registrada en la supervivencia al final del proceso de incubación.

Adjuvant effects of inhaled mono-2-ethylhexyl phthalate in BALB/cJ mice

DEFF Research Database (Denmark)

Hansen, Jitka Stilund; Larsen, Søren Thor; Poulsen, Lars K.

2007-01-01

Phthalates, including di(2-ethylhexyl) phthalate (DEHP), are widely used and have been linked with the development of wheezing and asthma. The main metabolite of DEHP, mono-2-ethylhexyl phthalate (MEHP), was investigated for adjuvant effects in a mouse inhalation model. BALB/cJ mice were exposed...... to aerosols of 0.03 or 0.4 mg/m(3) MEHP 5 days/week for 2 weeks and thereafter weekly for 12 weeks together with a low dose of ovalbumin (OVA) as a model allergen. Mice exposed to OVA alone or OVA+Al(OH)(3) served as negative and positive controls, respectively. Finally, all groups were exposed to a nebulized...... as of eosinophils in BAL fluid were observed. OVA-specific IgG1 production in both MEHP groups was significantly increased. OVA-specific IgE and IgG2a were not increased significantly. A dose-dependent increase in inflammatory cells was observed in BAL fluid, leading to significantly higher lymphocyte...

Fisetin-treatment alleviates airway inflammation through inhbition of MyD88/NF-κB signaling pathway.

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Huang, Wei; Li, Ming-Li; Xia, Ming-Yue; Shao, Jian-Ying

2018-07-01

Asthma is a common chronic airway inflammation disease and is considered as a major public health problem. Fisetin (3,3',4',7-tetrahydroxyflavone) is a naturally occurring flavonoid abundantly found in different vegetables and fruits. Fisetin has been reported to exhibit various positive biological effects, including anti-proliferative, anticancer, anti-oxidative and neuroprotective effects. We evaluated the effects of fisetin on allergic asthma regulation in mice. Mice were first sensitized, then airway-challenged with ovalbumin (OVA). Whether fisetin treatment attenuated OVA-induced airway inflammation was examined via inflammation inhibition through MyD88-related NF-κB (p65) signaling pathway. Mice were divided into the control (Con), OVA-induced asthma (Mod), 40 (FL) and 50 (FH) mg/kg fisetin-treated OVA-induced asthma groups. Our results found that OVA-induced airway inflammation in mice caused a significant inflammatory response via the activation of MyD88 and NF-κB signaling pathways, leading to release of pro-inflammatory cytokines. In contrast, fisetin-treated mice after OVA induction inhibited activation of MyD88 and NF-κB signaling pathways, resulting in downregulation of pro-inflammatory cytokine secretion. Further, fisetin significantly ameliorated the airway hyperresponsiveness (AHR) towards methacholine (Mch). In addition, fisetin reduced the number of eosinophil, monocyte, neutrophil and total white blood cell in the bronchoalveolar lavage fluid (BALF) of OVA-induced mice. The serum and BALF samples obtained from the OVA-induced mice with fisetin showed lower levels of pro-inflammatory cytokines. The results of our study illustrated that fisetin may be a new promising candidate to inhibit airway inflammation response induced by OVA.

Activated leucocyte cell adhesion molecule (ALCAM/CD166) regulates T cell responses in a murine model of food allergy.

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Kim, Y S; Kim, M N; Lee, K E; Hong, J Y; Oh, M S; Kim, S Y; Kim, K W; Sohn, M H

2018-05-01

Food allergy is a major public health problem. Studies have shown that long-term interactions between activated leucocyte cell adhesion molecule (ALCAM/CD166) on the surface of antigen-presenting cells, and CD6, a co-stimulatory molecule, influence immune responses. However, there are currently no studies on the functions of ALCAM in food allergy. Therefore, we aimed to identify the functions of ALCAM in ovalbumin (OVA)-induced food allergy using ALCAM-deficient mice. Wild-type (WT) and ALCAM-deficient (ALCAM -/- ) mice were sensitized intraperitoneally and with orally fed OVA. The mice were killed, and parameters related to food allergy and T helper type 2 (Th2) immune responses were analysed. ALCAM serum levels increased and mRNA expression decreased in OVA-challenged WT mice. Serum immunoglobulin (Ig)E levels, Th2 cytokine mRNA and histological injuries were higher in OVA-challenged WT mice than in control mice, and these were attenuated in ALCAM -/- mice. T cell proliferation of total cells, CD3 + CD4 + T cells and activated T cells in immune tissues were diminished in OVA-challenged ALCAM -/- mice. Proliferation of co-cultured T cells and dendritic cells (DCs) was decreased by the anti-CD6 antibody. In addition, WT mice sensitized by adoptive transfer of OVA-pulsed ALCAM -/- BM-derived DCs showed reduced immune responses. Lastly, serum ALCAM levels were higher in children with food allergy than in control subjects. In this study, serum levels of ALCAM were elevated in food allergy-induced WT mice and children with food allergy. Moreover, immune responses and T cell activation were attenuated in OVA-challenged ALCAM -/- mice. These results indicate that ALCAM regulates food allergy by affecting T cell activation. © 2018 British Society for Immunology.

Evaluation of patients with schistosomal portal hypertension treated in a tertiary hospital Perfil dos pacientes com Esquistossomose Mansoni tratados em hospital terciário

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Fábio Ferrari Makdissi

2009-12-01

Full Text Available BACKGROUND: Schistosomiasis is an important public health issue in more than 70 countries around the world. About 600 million people are at risk to acquire the parasite and there are 200 million infected worldwide. AIM: To evaluate the characteristics of schistosomal portal hypertension individuals who underwent previous esophageal varices bleeding treated in a tertiary hospital. METHODS: The records of 155 patients were evaluated and clinical, laboratorial, endoscopic, epidemiological features and hemorrhagic event severity were analyzed to individualize this population. RESULTS: Mean age was 37.2 years and no clinical signs of hepatic failure were observed. Serum laboratory tests to evaluate liver function were normal or slightly alter. Anemia was present in 70 %, leucopenia in 75 % and thrombocytopenia in 86 % of the patients. At endoscopic evaluation varices were classified as grade III and IV in 91.3 %; red spots were observed in 40.3 % and congestive gastropathy in 13.6 %. Patients presented a mean of 2.8 previous episodes of variceal hemorrhage and, in 75 % with hemodynamic instability. CONCLUSIONS: Patients with schistosomal portal hypertension and history of upper digestive bleeding from esophageal varices are young individuals, without either clinical or laboratorial evidence of liver dysfunction, that present high morbidity due to the severity of the acute event of bleeding.RACIONAL: Esquistossomose é importante doença na saúde pública envolvendo mais de 70 países. Cerca de 600 milhões de pessoas estão em áreas de risco para adquirir a doença e em torno de 200 milhões estão por ela infectados. OBJETIVO: Avaliar as características da hipertensão porta esquistossomótica em indivíduos que se submeteram previamente a tratamento de varizes esofágicas hemorrágicas em hospital terciário. MÉTODOS: Os prontuários de 155 pacientes foram avaliados analisando-se aspectos clínicos, laboratoriais, endoscópicos, epidemiol

Application of small RNA technology for improved control of parasitic helminths.

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Britton, Collette; Winter, Alan D; Marks, Neil D; Gu, Henry; McNeilly, Tom N; Gillan, Victoria; Devaney, Eileen

2015-08-15

Over the last decade microRNAs (miRNAs) and small interfering RNAs (siRNAs) have emerged as important regulators of post-transcriptional gene expression. miRNAs are short, non-coding RNAs that regulate a variety of processes including cancer, organ development and immune function. This class of small RNAs bind with partial complementarity to their target mRNA sequences, most often in the 3'UTR, to negatively regulate gene expression. In parasitic helminths, miRNAs are being increasingly studied for their potential roles in development and host-parasite interactions. The availability of genome data, combined with small RNA sequencing, has paved the way to profile miRNAs expressed at particular developmental stages for many parasitic helminths. While some miRNAs are conserved across species, others appear to be unique to specific parasites, suggesting important roles in adaptation and survival in the host environment. Some miRNAs are released from parasites, in exosomes or in protein complexes, and the potential effects of these on host immune function are being increasingly studied. In addition, release of miRNAs from schistosome and filarial parasites into host plasma can be exploited for the development of specific and sensitive diagnostic biomarkers of infection. Interfering with miRNA function, as well as silencing key components of the pathways they regulate, will progress our understanding of parasite development and provide a novel approach to therapeutic control. RNA interference (RNAi) by siRNAs has proven to be inconsistent in parasitic nematodes. However, the recent successes reported for schistosome and liver fluke RNAi, encourage further efforts to enhance delivery of RNA and improve in vitro culture systems and assays to monitor phenotypic effects in nematodes. These improvements are important for the establishment of reliable functional genomic platforms for novel drug and vaccine development. In this review we focus on the important roles of mi

Prevalence and effect of schistosome and soil-transmitted helminth infection on labour input in rice-growing communities of Ogun State, Nigeria

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Sammy Olufemi Sam-Wobo

2013-06-01

Full Text Available Schistosomiasis and soil-transmitted helminthiasis (STH are public health problems in communities which lack basic social amenities with poor hygienic conditions. Studies were carried out to determine the prevalence and effect of schistosomes and soil-transmitted helminths infection on labour input on rice production in 9 rice-growing communities of Ogun State. Parasitological examinations of urine and faecal samples, and structured questionnaires were conducted on 243 consented individuals from May 2009 to March 2010. The results showed an overall prevalence of 17% for Ascaris lumbricoides, 12% for hookworms, 2% for Trichuris trichiura, 1% for Schistosoma haematobium and 1% for Schistosoma mansoni. A. lumbricoides and hookworms were more prevalent in Agbajege (25%, and varied in the other 8 communities. T. trichiura was prevalent in three communities, Agbajege (5%, Akodu (4.2%, and Moloko-Asipa (4.8 %; S. haematobium was prevalent only in Ayedere (2.6% and Lufoko (8%, while S. mansoni was prevalent only in Moloko-Asipa (9.5%. Infections among the gender were varied as 26.3 % of males and 33.8 % of females had an overall prevalence of: A. lumbricoides (16.8%, hookworms (11.8%, T. trichiura (1.6%, S. haematobium (1.1% and S. mansoni (1.1%. On frequency of infection to incapacitation per year, 45% of respondents were incapacitated 1-2 times, 27% 3-4 times and 19% were incapacitated more than 4 times. Understanding the effect of these two diseases will not only improve the health status of residents but also increase their productivity and ensure food security.

The relationship between water, sanitation and schistosomiasis: a systematic review and meta-analysis.

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Jack E T Grimes

2014-12-01

Full Text Available Access to "safe" water and "adequate" sanitation are emphasized as important measures for schistosomiasis control. Indeed, the schistosomes' lifecycles suggest that their transmission may be reduced through safe water and adequate sanitation. However, the evidence has not previously been compiled in a systematic review.We carried out a systematic review and meta-analysis of studies reporting schistosome infection rates in people who do or do not have access to safe water and adequate sanitation. PubMed, Web of Science, Embase, and the Cochrane Library were searched from inception to 31 December 2013, without restrictions on year of publication or language. Studies' titles and abstracts were screened by two independent assessors. Papers deemed of interest were read in full and appropriate studies included in the meta-analysis. Publication bias was assessed through the visual inspection of funnel plots and through Egger's test. Heterogeneity of datasets within the meta-analysis was quantified using Higgins' I2.Safe water supplies were associated with significantly lower odds of schistosomiasis (odds ratio (OR = 0.53, 95% confidence interval (CI: 0.47-0.61. Adequate sanitation was associated with lower odds of Schistosoma mansoni, (OR = 0.59, 95% CI: 0.47-0.73 and Schistosoma haematobium (OR = 0.69, 95% CI: 0.57-0.84. Included studies were mainly cross-sectional and quality was largely poor.Our systematic review and meta-analysis suggests that increasing access to safe water and adequate sanitation are important measures to reduce the odds of schistosome infection. However, most of the studies were observational and quality was poor. Hence, there is a pressing need for adequately powered cluster randomized trials comparing schistosome infection risk with access to safe water and adequate sanitation, more studies which rigorously define water and sanitation, and new research on the relationships between water, sanitation, hygiene, human

The relationship between water, sanitation and schistosomiasis: a systematic review and meta-analysis.

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Grimes, Jack E T; Croll, David; Harrison, Wendy E; Utzinger, Jürg; Freeman, Matthew C; Templeton, Michael R

2014-12-01

Access to "safe" water and "adequate" sanitation are emphasized as important measures for schistosomiasis control. Indeed, the schistosomes' lifecycles suggest that their transmission may be reduced through safe water and adequate sanitation. However, the evidence has not previously been compiled in a systematic review. We carried out a systematic review and meta-analysis of studies reporting schistosome infection rates in people who do or do not have access to safe water and adequate sanitation. PubMed, Web of Science, Embase, and the Cochrane Library were searched from inception to 31 December 2013, without restrictions on year of publication or language. Studies' titles and abstracts were screened by two independent assessors. Papers deemed of interest were read in full and appropriate studies included in the meta-analysis. Publication bias was assessed through the visual inspection of funnel plots and through Egger's test. Heterogeneity of datasets within the meta-analysis was quantified using Higgins' I2. Safe water supplies were associated with significantly lower odds of schistosomiasis (odds ratio (OR) = 0.53, 95% confidence interval (CI): 0.47-0.61). Adequate sanitation was associated with lower odds of Schistosoma mansoni, (OR = 0.59, 95% CI: 0.47-0.73) and Schistosoma haematobium (OR = 0.69, 95% CI: 0.57-0.84). Included studies were mainly cross-sectional and quality was largely poor. Our systematic review and meta-analysis suggests that increasing access to safe water and adequate sanitation are important measures to reduce the odds of schistosome infection. However, most of the studies were observational and quality was poor. Hence, there is a pressing need for adequately powered cluster randomized trials comparing schistosome infection risk with access to safe water and adequate sanitation, more studies which rigorously define water and sanitation, and new research on the relationships between water, sanitation, hygiene, human behavior

Ovalbumin with Glycated Carboxyl Groups Shows Membrane-Damaging Activity

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Ching-Chia Tang

2017-02-01

Full Text Available The aim of the present study was to investigate whether glycated ovalbumin (OVA showed novel activity at the lipid-water interface. Mannosylated OVA (Man-OVA was prepared by modification of the carboxyl groups with p-aminophenyl α-dextro (d-mannopyranoside. An increase in the number of modified carboxyl groups increased the membrane-damaging activity of Man-OVA on cell membrane-mimicking vesicles, whereas OVA did not induce membrane permeability in the tested phospholipid vesicles. The glycation of carboxyl groups caused a notable change in the gross conformation of OVA. Moreover, owing to their spatial positions, the Trp residues in Man-OVA were more exposed, unlike those in OVA. Fluorescence quenching studies suggested that the Trp residues in Man-OVA were located on the interface binds with the lipid vesicles, and their microenvironment was abundant in positively charged residues. Although OVA and Man-OVA showed a similar binding affinity for lipid vesicles, the lipid-interacting feature of Man-OVA was distinct from that of OVA. Chemical modification studies revealed that Lys and Arg residues, but not Trp residues, played a crucial role in the membrane-damaging activity of Man-OVA. Taken together, our data suggest that glycation of carboxyl groups causes changes in the structural properties and membrane-interacting features of OVA, generating OVA with membrane-perturbing activities at the lipid-water interface.

Microarray analysis of gene expression profiles of Schistosoma japonicum derived from less-susceptible host water buffalo and susceptible host goat.

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Jianmei Yang

Full Text Available BACKGROUND: Water buffalo and goats are natural hosts for S. japonicum in endemic areas of China. The susceptibility of these two hosts to schistosome infection is different, as water buffalo are less conducive to S. japonicum growth and development. To identify genes that may affect schistosome development and survival, we compared gene expression profiles of schistosomes derived from these two natural hosts using high-throughput microarray technology. RESULTS: The worm recovery rate was lower and the length and width of worms from water buffalo were smaller compared to those from goats following S. japonicum infection for 7 weeks. Besides obvious morphological difference between the schistosomes derived from the two hosts, differences were also observed by scanning and transmission electron microscopy. Microarray analysis showed differentially expressed gene patterns for parasites from the two hosts, which revealed that genes related to lipid and nucleotide metabolism, as well as protein folding, sorting, and degradation were upregulated, while others associated with signal transduction, endocrine function, development, immune function, endocytosis, and amino acid/carbohydrate/glycan metabolism were downregulated in schistosomes from water buffalo. KEGG pathway analysis deduced that the differentially expressed genes mainly involved lipid metabolism, the MAPK and ErbB signaling pathways, progesterone-mediated oocyte maturation, dorso-ventral axis formation, reproduction, and endocytosis, etc. CONCLUSION: The microarray gene analysis in schistosomes derived from water buffalo and goats provide a useful platform to disclose differences determining S. japonicum host compatibility to better understand the interplay between natural hosts and parasites, and identify schistosome target genes associated with susceptibility to screen vaccine candidates.

Enhanced immunization via dissolving microneedle array-based delivery system incorporating subunit vaccine and saponin adjuvant.

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Zhao, Ji-Hui; Zhang, Qi-Bo; Liu, Bao; Piao, Xiang-Hua; Yan, Yu-Lu; Hu, Xiao-Ge; Zhou, Kuan; Zhang, Yong-Tai; Feng, Nian-Ping

2017-01-01

To enhance the immunogenicity of the model subunit vaccine, ovalbumin (OVA) was combined with platycodin (PD), a saponin adjuvant. To reduce the toxicity of PD, OVA, and adjuvant were loaded together into liposomes before being incorporated into a dissolving microneedle array. OVA- and PD-loaded liposomes (OVA-PD-Lipos) were prepared using the film dispersion method. Their uptake behavior, toxicity to mouse bone marrow dendritic cells (BMDCs), and hemolytic activity to rabbit red blood cells (RBCs) were evaluated. The OVA-PD-Lipos were incorporated into a dissolving microneedle array. The chemical stability of OVA and the physical stability of OVA-PD-Lipos in microneedle arrays were investigated. The immune response of Institute of Cancer Research mice and potential skin irritation reaction of rabbits to OVA-PD-Lipos-MNs were evaluated. The uptake of OVA by mouse BMDCs was greatly enhanced when OVA was prepared as OVA-PD-Lipos, and in this form, the toxicity of PD was dramatically reduced. OVA was chemically stable as OVA-PD-Lipos, when OVA-PD-Lipos was incorporated into a dissolving microneedle array. Institute of Cancer Research mice treated with OVA-PD-Lipos-MNs showed a significantly enhanced immune response. PD combined with OVA elicited a balanced Th1 and Th2 humoral immune response in mice, with minimal irritation in rabbit skin. The dissolving microneedle array-based system is a promising delivery vehicle for subunit vaccine and its adjuvant.

Mesoporous Silica Nanoparticle-Coated Microneedle Arrays for Intradermal Antigen Delivery.

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Tu, Jing; Du, Guangsheng; Reza Nejadnik, M; Mönkäre, Juha; van der Maaden, Koen; Bomans, Paul H H; Sommerdijk, Nico A J M; Slütter, Bram; Jiskoot, Wim; Bouwstra, Joke A; Kros, Alexander

2017-08-01

To develop a new intradermal antigen delivery system by coating microneedle arrays with lipid bilayer-coated, antigen-loaded mesoporous silica nanoparticles (LB-MSN-OVA). Synthesis of MSNs with 10-nm pores was performed and the nanoparticles were loaded with the model antigen ovalbumin (OVA), and coated with a lipid bilayer (LB-MSN-OVA). The uptake of LB-MSN-OVA by bone marrow-derived dendritic cells (BDMCs) was studied by flow cytometry. The designed LB-MSN-OVA were coated onto pH-sensitive pyridine-modified microneedle arrays and the delivery of LB-MSN-OVA into ex vivo human skin was studied. The synthesized MSNs demonstrated efficient loading of OVA with a maximum loading capacity of about 34% and the lipid bilayer enhanced the colloidal stability of the MSNs. Uptake of OVA loaded in LB-MSN-OVA by BMDCs was higher than that of free OVA, suggesting effective targeting of LB-MSN-OVA to antigen-presenting cells. Microneedles were readily coated with LB-MSN-OVA at pH 5.8, yielding 1.5 μg of encapsulated OVA per microneedle array. Finally, as a result of the pyridine modification, LB-MSN-OVA were effectively released from the microneedles upon piercing the skin. Microneedle arrays coated with LB-MSN-OVA were successfully developed and shown to be suitable for intradermal delivery of the encapsulated protein antigen.

MicroRNAs Are Involved in the Regulation of Ovary Development in the Pathogenic Blood Fluke Schistosoma japonicum.

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Lihui Zhu

2016-02-01

Full Text Available Schistosomes, blood flukes, are an important global public health concern. Paired adult female schistosomes produce large numbers of eggs that are primarily responsible for the disease pathology and critical for dissemination. Consequently, understanding schistosome sexual maturation and egg production may open novel perspectives for intervening with these processes to prevent clinical symptoms and to interrupt the life-cycle of these blood-flukes. microRNAs (miRNAs are key regulators of many biological processes including development, cell proliferation, metabolism, and signal transduction. Here, we report on the identification of Schistosoma japonicum miRNAs using small RNA deep sequencing in the key stages of male-female pairing, gametogenesis, and egg production. We identified 38 miRNAs, including 10 previously unknown miRNAs. Eighteen of the miRNAs were differentially expressed between male and female schistosomes and during different stages of sexual maturation. We identified 30 potential target genes for 16 of the S. japonicum miRNAs using antibody-based pull-down assays and bioinformatic analyses. We further validated some of these target genes using either in vitro luciferase assays or in vivo miRNA suppression experiments. Notably, suppression of the female enriched miRNAs bantam and miR-31 led to morphological alteration of ovaries in female schistosomes. These findings uncover key roles for specific miRNAs in schistosome sexual maturation and egg production.

MicroRNAs Are Involved in the Regulation of Ovary Development in the Pathogenic Blood Fluke Schistosoma japonicum.

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Zhu, Lihui; Zhao, Jiangping; Wang, Jianbin; Hu, Chao; Peng, Jinbiao; Luo, Rong; Zhou, Chunjing; Liu, Juntao; Lin, Jiaojiao; Jin, Youxin; Davis, Richard E; Cheng, Guofeng

2016-02-01

Schistosomes, blood flukes, are an important global public health concern. Paired adult female schistosomes produce large numbers of eggs that are primarily responsible for the disease pathology and critical for dissemination. Consequently, understanding schistosome sexual maturation and egg production may open novel perspectives for intervening with these processes to prevent clinical symptoms and to interrupt the life-cycle of these blood-flukes. microRNAs (miRNAs) are key regulators of many biological processes including development, cell proliferation, metabolism, and signal transduction. Here, we report on the identification of Schistosoma japonicum miRNAs using small RNA deep sequencing in the key stages of male-female pairing, gametogenesis, and egg production. We identified 38 miRNAs, including 10 previously unknown miRNAs. Eighteen of the miRNAs were differentially expressed between male and female schistosomes and during different stages of sexual maturation. We identified 30 potential target genes for 16 of the S. japonicum miRNAs using antibody-based pull-down assays and bioinformatic analyses. We further validated some of these target genes using either in vitro luciferase assays or in vivo miRNA suppression experiments. Notably, suppression of the female enriched miRNAs bantam and miR-31 led to morphological alteration of ovaries in female schistosomes. These findings uncover key roles for specific miRNAs in schistosome sexual maturation and egg production.

Experimental pulmonary schistosomiasis: lack of morphological evidence of modulation in schistosomal pulmonary granulomas Esquistossomose pulmonar experimental: falta de evidência morfológica de modulação nos granulomas esquistosomóticos pulmonares

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Maura R. F. Souza Vidal

1993-10-01

Full Text Available Numerous pulmonary schistosome egg granulomas were present in mice submitted to partial portal vein ligation (Warren's model. The granulomas were characterized by cellular aggregations formed within alveolar tissue. Main cellular types were macrophages (epithelioid cells, eosinophils, plasma cells and lymphocytes. These cells were supported by scanty fibrous stroma and exhibited close membrane contact points amongst themselves, but without forming specialized adhesion apparatus. When granulomas involved arterial structures, proliferation of cndothelial and smooth muscle cells occurred and fibrosis associated with angiogenesis became more evident. Granulomas formed around mature eggs in the pulmonary alveolar tissue presented approximately the same size and morphology regardless of the time of infection, the latter being 10, 18 and 25 weeks after cercarial exposure. This persistence of morphological appearance suggests that pulmonary granulomas do not undergo immunological modulation, as is the case with the granulomas in the liver and, to a lesser extent, in the intestines. Probably, besides general immunological factors, local (stromal factors play an important role in schistosomal granuloma modulation.Em camundongos submetidos à ligadura parcial da veia porta e infecção pelo Schistosoma mansoni, os granulomas periovulares apareceram em grande número nos pulmões, comprovando a validade do modelo de Warren. Histologicamente os granulomas eram representados por agregados celulares compactos no seio de escasso estroma. Os macrófagos (células epitelióides e eosinófilos eram os elementos celulares predominantes, vindo em seguida os linfóticos e plasmócitos. Ultraestruturalmenle, as células do granuloma exibiam íntimo contacto de suas membranas, com varios pontos de adesão, mas sem formar estruturas juncionais mais específicas. Os granulomas formados em torno a ovos maduros tinham tamanho, forma e composição celular similares ap

Placental restriction of fetal growth reduces cutaneous responses to antigen after sensitization in sheep.

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Wooldridge, Amy L; Bischof, Robert J; Meeusen, Els N; Liu, Hong; Heinemann, Gary K; Hunter, Damien S; Giles, Lynne C; Kind, Karen L; Owens, Julie A; Clifton, Vicki L; Gatford, Kathryn L

2014-04-01

Prenatal and early childhood exposures are implicated as causes of allergy, but the effects of intrauterine growth restriction on immune function and allergy are poorly defined. We therefore evaluated effects of experimental restriction of fetal growth on immune function and allergic sensitization in adolescent sheep. Immune function (circulating total red and white blood cells, neutrophils, lymphocytes, monocytes, eosinophils, and basophils, and the antibody response to Clostridial vaccination) and responses to house dust mite (HDM) allergen and ovalbumin (OVA) antigen sensitization (specific total Ig, IgG1, and IgE antibodies, and cutaneous hypersensitivity) were investigated in adolescent sheep from placentally restricted (PR, n = 23) and control (n = 40) pregnancies. Increases in circulating HDM-specific IgE (P = 0.007) and OVA-specific IgE (P = 0.038) were greater in PR than control progeny. PR did not alter total Ig, IgG1, or IgM responses to either antigen. PR increased OVA-specific but not HDM-specific IgA responses in females only (P = 0.023). Multiple birth increased Ig responses to OVA in a sex-specific manner. PR decreased the proportion of positive cutaneous hypersensitivity responders to OVA at 24 h (P = 0.030) but had no effect on cutaneous responses to HDM. Acute wheal responses to intradermal histamine correlated positively with birth weight in singletons (P = 0.023). Intrauterine growth restriction may suppress inflammatory responses in skin downstream of IgE induction, without impairment in antibody responses to a nonpolysaccharide vaccine. Discord between cutaneous and IgE responses following sensitization suggests new mechanisms for prenatal allergy programming.

Induction of antigen-specific immunity by pH-sensitive carbonate apatite as a potent vaccine carrier

International Nuclear Information System (INIS)

Hebishima, Takehisa; Tada, Seiichi; Takeshima, Shin-nosuke; Akaike, Toshihiro; Ito, Yoshihiro; Aida, Yoko

2011-01-01

Highlights: ► To develop effective vaccine, we examined the effects of CO 3 Ap as an antigen carrier. ► OVA contained in CO 3 Ap was taken up by BMDCs more effectively than free OVA. ► OVA-immunized splenocytes was activated by OVA contained in CO 3 Ap effectively. ► OVA contained in CO 3 Ap induced strong OVA-specific immune responses to C57BL/6 mice. ► CO 3 Ap is promising antigen carrier for the achievement of effective vaccine. -- Abstract: The ability of carbonate apatite (CO 3 Ap) to enhance antigen-specific immunity was examined in vitro and in vivo to investigate its utility as a vaccine carrier. Murine bone marrow-derived dendritic cells took up ovalbumin (OVA) containing CO 3 Ap more effectively than free OVA. Interestingly, mice immunized with OVA-containing CO 3 Ap produced OVA-specific antibodies more effectively than mice immunized with free OVA. Furthermore, immunization of C57BL/6 mice with OVA-containing CO 3 Ap induced the proliferation and antigen-specific production of IFN-γ by splenocytes more strongly than immunization with free OVA. Moreover, no significant differences were detected in the induction of delayed-type hypersensitivity responses, an immune reaction involving an antigen-specific, cell-mediated immune response between OVA-containing CO 3 Ap and OVA-containing alumina salt (Alum), suggesting that CO 3 Ap induced cell-mediated immune response to the same degree as Alum, which is commonly used for clinical applications. This study is the first to demonstrate the induction of antigen-specific immune responses in vivo by CO 3 Ap.

The small RNA complement of adult Schistosoma haematobium.

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Andreas J Stroehlein

2018-05-01

Full Text Available Blood flukes of the genus Schistosoma cause schistosomiasis-a neglected tropical disease (NTD that affects more than 200 million people worldwide. Studies of schistosome genomes have improved our understanding of the molecular biology of flatworms, but most of them have focused largely on protein-coding genes. Small non-coding RNAs (sncRNAs have been explored in selected schistosome species and are suggested to play essential roles in the post-transcriptional regulation of genes, and in modulating flatworm-host interactions. However, genome-wide small RNA data are currently lacking for key schistosomes including Schistosoma haematobium-the causative agent of urogenital schistosomiasis of humans.MicroRNAs (miRNAs and other sncRNAs of male and female adults of S. haematobium and small RNA transcription levels were explored by deep sequencing, genome mapping and detailed bioinformatic analyses.In total, 89 transcribed miRNAs were identified in S. haematobium-a similar complement to those reported for the congeners S. mansoni and S. japonicum. Of these miRNAs, 34 were novel, with no homologs in other schistosomes. Most miRNAs (n = 64 exhibited sex-biased transcription, suggestive of roles in sexual differentiation, pairing of adult worms and reproductive processes. Of the sncRNAs that were not miRNAs, some related to the spliceosome (n = 21, biogenesis of other RNAs (n = 3 or ribozyme functions (n = 16, whereas most others (n = 3798 were novel ('orphans' with unknown functions.This study provides the first genome-wide sncRNA resource for S. haematobium, extending earlier studies of schistosomes. The present work should facilitate the future curation and experimental validation of sncRNA functions in schistosomes to enhance our understanding of post-transcriptional gene regulation and of the roles that sncRNAs play in schistosome reproduction, development and parasite-host cross-talk.

The small RNA complement of adult Schistosoma haematobium.

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Stroehlein, Andreas J; Young, Neil D; Korhonen, Pasi K; Hall, Ross S; Jex, Aaron R; Webster, Bonnie L; Rollinson, David; Brindley, Paul J; Gasser, Robin B

2018-05-01

Blood flukes of the genus Schistosoma cause schistosomiasis-a neglected tropical disease (NTD) that affects more than 200 million people worldwide. Studies of schistosome genomes have improved our understanding of the molecular biology of flatworms, but most of them have focused largely on protein-coding genes. Small non-coding RNAs (sncRNAs) have been explored in selected schistosome species and are suggested to play essential roles in the post-transcriptional regulation of genes, and in modulating flatworm-host interactions. However, genome-wide small RNA data are currently lacking for key schistosomes including Schistosoma haematobium-the causative agent of urogenital schistosomiasis of humans. MicroRNAs (miRNAs) and other sncRNAs of male and female adults of S. haematobium and small RNA transcription levels were explored by deep sequencing, genome mapping and detailed bioinformatic analyses. In total, 89 transcribed miRNAs were identified in S. haematobium-a similar complement to those reported for the congeners S. mansoni and S. japonicum. Of these miRNAs, 34 were novel, with no homologs in other schistosomes. Most miRNAs (n = 64) exhibited sex-biased transcription, suggestive of roles in sexual differentiation, pairing of adult worms and reproductive processes. Of the sncRNAs that were not miRNAs, some related to the spliceosome (n = 21), biogenesis of other RNAs (n = 3) or ribozyme functions (n = 16), whereas most others (n = 3798) were novel ('orphans') with unknown functions. This study provides the first genome-wide sncRNA resource for S. haematobium, extending earlier studies of schistosomes. The present work should facilitate the future curation and experimental validation of sncRNA functions in schistosomes to enhance our understanding of post-transcriptional gene regulation and of the roles that sncRNAs play in schistosome reproduction, development and parasite-host cross-talk.

Comparing macrophyte herbivory by introduced Louisiana crayfish ...

African Journals Online (AJOL)

The omnivorous Louisiana crayfish, Procambarus clarkii, has caused significant changes to macrophyte communities worldwide and may have similar negative effects in Kenya if used as a biological control agent for snails harbouring human schistosomes. Here we examine how herbivory by the introduced Louisiana ...

Artemisia argyi attenuates airway inflammation in ovalbumin-induced asthmatic animals.

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Shin, Na-Rae; Ryu, Hyung-Won; Ko, Je-Won; Park, Sung-Hyeuk; Yuk, Heung-Joo; Kim, Ha-Jung; Kim, Jong-Choon; Jeong, Seong-Hun; Shin, In-Sik

2017-09-14

Artemisia argyi is a traditional herbal medicine in Korea and commonly called as mugwort. It is traditionally used as food source and tea to control abdominal pain, dysmenorrhea, uterine hemorrhage, and inflammation. We investigated the effects of A. argyi (TOTAL) and dehydromatricarin A (DA), its active component on ovalbumin (OVA)-induced allergic asthma. The animals were sensitized on day 0 and 14 by intraperitoneal injection of OVA with aluminum hydroxide. On day 21, 22 and 23 after the initial sensitization, the animals received an airway challenge with OVA for 1h using an ultrasonic nebulizer. TOTAL (50 and 100mg/kg) or DA (10 and 20mg/kg) were administered to mice by oral gavage once daily from day 18-23. Airway hyperresponsiveness (AHR) was measured 24h after final OVA challenge. TOTAL and DA treated animals reduced inflammatory cell counts, cytokines and AHR in asthmatic animals, which was accompanied with inflammatory cell accumulation and mucus hypersecretion. Furthermore, TOTAL and DA significantly declined Erk phosphorylation and the expression of MMP-9 in asthmatic animals. In conclusion, we indicate that Total and DA suppress allergic inflammatory responses caused by OVA challenge. It was considered that A. argyi has a potential for treating allergic asthma. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

IRF8-dependent DCs play a key role in the regulation of CD8 T cell responses to epithelial-derived antigen in the steady state but not in inflammation

DEFF Research Database (Denmark)

Joeris, Thorsten

Along the process of epithelial self-renewal, antigens derived from apoptotic intestinal epithelial cells (IECs) are taken up by antigen presenting cells (APCs), transported to gut-draining lymph nodes and crosspresented to CD8 T cells. In steady state, rapid tolerization of CD8 T cells reactive...... towards epithelialderived antigens is crucial to maintain tissue homeostasis. Since IRF8-dependent dendritic dells (IRF8-DCs) have superior cross-presenting capabilities, we aimed to investigate their role in this process. IFABP-tOva mice, expressing the model-antigen Ovalbumin (Ova) in IECs, were used...... as recipients to set up chimeras using either CD11c-cre.Irf8fl/fl bone marrow, which cannot generate IRF8-DCs, or cre-negative Irf8fl/fl control bone marrow. Whereas transfer of Ova-specific CD8 T cells (OT-I cells) to control chimeras resulted in their rapid tolerization, OT-I cells transferred to CD11c...

IgA attenuates anaphylaxis and subsequent immune responses in mice: possible application of IgA to vaccines.

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Yamaki, Kouya; Nakashima, Takayuki; Miyatake, Kenji; Ishibashi, Yuki; Ito, Ayaka; Kuranishi, Ayu; Taguchi, Akihito; Morioka, Ayumi; Yamamoto, Midori; Yoshino, Shin

2014-01-01

Administration of the influenza vaccination to patients with an egg allergy is major health concern. Contaminating egg antigens occasionally induce severe anaphylactic shock in these patients following administration of the vaccination; therefore, the development of a safer vaccination is needed. In the present study, we investigated whether a mixture of four newly and previously generated anti-ovalbumin (OVA) IgA monoclonal antibodies (mAbs) could inhibit both anaphylactic shock upon a subcutaneous OVA challenge and subsequent further sensitization against OVA in passively anti-OVA IgE-sensitized mice and actively sensitized mice with an injection of OVA. The prevention of anaphylaxis by anti-OVA IgA mAbs was suggested to be mediated through the inhibition of OVA binding to allergenic antibodies such as anti-OVA IgE on mast cells and deceleration of the rate of OVA penetration from the injected site into the systemic circulation. Anti-OVA IgA mAbs inhibited further sensitization against OVA in mice actively sensitized with OVA, but did not affect sensitization against the unrelated antigen, phosphorylcholine-keyhole limpet hemocyanin co-injected with OVA. Our findings indicate that adding the anti-egg antigen IgA to the influenza vaccine should reduce not only the risk of inducing anaphylactic shock, but also undesired further sensitization against egg antigens following the vaccination without affecting the intended beneficial effect of the vaccine, namely the upregulation of immune responses to influenza viruses.

Description of the ova and ovipositional strategies of six sterrhine taxa from Madrid, including comparative data with other species of this subfamily (Lepidoptera: Geometridae: Sterrhinae

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King, Gareth Edward

2016-06-01

Full Text Available Original data are presented which describe ova of the following six taxa in the Sterrhinae Meyrick, 1892: Idaea litigiosaria (Boisduval, 1840, Idaea sericeata calvaria Wehrli, 1927, Idaea ochrata albida (Zerny, 1936, Idaea incisaria (Staudinger, 1892, Idaea cervantaria (Millière, 1869 and >em>Scopula (Glossotrophia asellaria dentatolineata Wehrli, 1926. Subsequent analysis of SEM imaging provides data related to the chorion structure, as well as that associated with the strategies adopted by females at oviposition under laboratory conditions; comparative data are provided of other European sterrhines.Se presentan datos inéditos que describen los huevos de los siguientes taxones de Sterrhinae Meyrick, 1892: Idaea litigiosaria (Boisduval, 1840, Idaea sericeata calvaria Wehrli, 1927, Idaea ochrata albida (Zerny, 1936, Idaea incisaria (Staudinger, 1892, Idaea cervantaria (Millière, 1869 and Scopula (Glossotrophia asellaria dentatolineata Wehrli, 1926. Se ofrece un análisis pormenorizado de las imágenes MEB en cuanto a la estructura del corión se refiere, además de una descripción de las estrategias de la puesta adoptadas por parte de las hembras en condiciones de laboratorio. Se ofrecen datos comparativos con otras especies europeas de Sterrhinae.

Enhanced immunization via dissolving microneedle array-based delivery system incorporating subunit vaccine and saponin adjuvant

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Zhao JH

2017-07-01

Full Text Available Ji-Hui Zhao,1,* Qi-Bo Zhang,1,* Bao Liu,2 Xiang-Hua Piao,1 Yu-Lu Yan,1 Xiao-Ge Hu,1 Kuan Zhou,1 Yong-Tai Zhang,1 Nian-Ping Feng1 1School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Anethesiology Department, Augusta University, Augusta, GA, USA *These authors contributed equally to this work Purpose: To enhance the immunogenicity of the model subunit vaccine, ovalbumin (OVA was combined with platycodin (PD, a saponin adjuvant. To reduce the toxicity of PD, OVA, and adjuvant were loaded together into liposomes before being incorporated into a dissolving microneedle array.Methods: OVA- and PD-loaded liposomes (OVA-PD-Lipos were prepared using the film dispersion method. Their uptake behavior, toxicity to mouse bone marrow dendritic cells (BMDCs, and hemolytic activity to rabbit red blood cells (RBCs were evaluated. The OVA-PD-Lipos were incorporated into a dissolving microneedle array. The chemical stability of OVA and the physical stability of OVA-PD-Lipos in microneedle arrays were investigated. The immune response of Institute of Cancer Research mice and potential skin irritation reaction of rabbits to OVA-PD-Lipos-MNs were evaluated.Results: The uptake of OVA by mouse BMDCs was greatly enhanced when OVA was prepared as OVA-PD-Lipos, and in this form, the toxicity of PD was dramatically reduced. OVA was chemically stable as OVA-PD-Lipos, when OVA-PD-Lipos was incorporated into a dissolving microneedle array. Institute of Cancer Research mice treated with OVA-PD-Lipos-MNs showed a significantly enhanced immune response. PD combined with OVA elicited a balanced Th1 and Th2 humoral immune response in mice, with minimal irritation in rabbit skin.Conclusion: The dissolving microneedle array-based system is a promising delivery vehicle for subunit vaccine and its adjuvant. Keywords: subunit vaccine, saponin adjuvant, liposomes, dissolving microneedle array, intradermal vaccination

Beneficial effects of ursodeoxycholic acid via inhibition of airway remodelling, apoptosis of airway epithelial cells, and Th2 immune response in murine model of chronic asthma.

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Işık, S; Karaman, M; Çilaker Micili, S; Çağlayan-Sözmen, Ş; Bağrıyanık, H Alper; Arıkan-Ayyıldız, Z; Uzuner, N; Karaman, Ö

In previous studies, anti-inflammatory, anti-apoptotic and immunomodulatory effects of ursodeoxycholic acid (UDCA) on liver diseases have been shown. In this study, we aimed to investigate the effects of UDCA on airway remodelling, epithelial apoptosis, and T Helper (Th)-2 derived cytokine levels in a murine model of chronic asthma. Twenty-seven BALB/c mice were divided into five groups; PBS-Control, OVA-Placebo, OVA-50mg/kg UDCA, OVA-150mg/kg UDCA, OVA-Dexamethasone. Mice in groups OVA-50mg/kg UDCA, OVA-150mg/kg UDCA, OVA-Dexamethasone received the UDCA (50mg/kg), UDCA (150mg/kg), and dexamethasone, respectively. Epithelium thickness, sub-epithelial smooth muscle thickness, number of mast and goblet cells of samples isolated from the lung were measured. Immunohistochemical scorings of the lung tissue for matrix metalloproteinase-9 (MMP-9), vascular endothelial growth factor (VEG-F), transforming growth factor-beta (TGF-β), terminal deoxynucleotidyl transferase-mediated dUTP nick endlabeling (TUNEL) and cysteine-dependent aspartate-specific proteases (caspase)-3 were determined. IL-4, IL-5, IL-13, Nitric oxide, ovalbumin-specific immunoglobulin (Ig) E levels were quantified. The dose of 150mg/kg UDCA treatment led to lower epithelial thickness, sub-epithelial smooth muscle thickness, goblet and mast cell numbers compared to placebo. Except for MMP-9 and TUNEL all immunohistochemical scores were similar in both UDCA treated groups and the placebo. All cytokine levels were significantly lower in group IV compared to the placebo. These findings suggested that the dose of 150mg/kg UDCA improved all histopathological changes of airway remodelling and its beneficial effects might be related to modulating Th-2 derived cytokines and the inhibition of apoptosis of airway epithelial cells. Copyright © 2017 SEICAP. Published by Elsevier España, S.L.U. All rights reserved.

Allergen-specific Th1 cells counteract efferent Th2 cell-dependent bronchial hyperresponsiveness and eosinophilic inflammation partly via IFN-gamma.

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Huang, T J; MacAry, P A; Eynott, P; Moussavi, A; Daniel, K C; Askenase, P W; Kemeny, D M; Chung, K F

2001-01-01

Th2 T cell immune-driven inflammation plays an important role in allergic asthma. We studied the effect of counterbalancing Th1 T cells in an asthma model in Brown Norway rats that favors Th2 responses. Rats received i.v. transfers of syngeneic allergen-specific Th1 or Th2 cells, 24 h before aerosol exposure to allergen, and were studied 18-24 h later. Adoptive transfer of OVA-specific Th2 cells, but not Th1 cells, and OVA, but not BSA exposure, induced bronchial hyperresponsiveness (BHR) to acetylcholine and eosinophilia in a cell number-dependent manner. Importantly, cotransfer of OVA-specific Th1 cells dose-dependently reversed BHR and bronchoalveolar lavage (BAL) eosinophilia, but not mucosal eosinophilia. OVA-specific Th1 cells transferred alone induced mucosal eosinophilia, but neither BHR nor BAL eosinophilia. Th1 suppression of BHR and BAL eosinophilia was allergen specific, since cotransfer of BSA-specific Th1 cells with the OVA-specific Th2 cells was not inhibitory when OVA aerosol alone was used, but was suppressive with OVA and BSA challenge. Furthermore, recipients of Th1 cells alone had increased gene expression for IFN-gamma in the lungs, while those receiving Th2 cells alone showed increased IL-4 mRNA. Importantly, induction of these Th2 cytokines was inhibited in recipients of combined Th1 and Th2 cells. Anti-IFN-gamma treatment attenuated the down-regulatory effect of Th1 cells. Allergen-specific Th1 cells down-regulate efferent Th2 cytokine-dependent BHR and BAL eosinophilia in an asthma model via mechanisms that depend on IFN-gamma. Therapy designed to control the efferent phase of established asthma by augmenting down-regulatory Th1 counterbalancing mechanisms should be effective.

Schistosomiasis in Lake Malawi villages

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Madsen, Henry; Bloch, Paul; Makaula, Peter

2011-01-01

Historically, open shorelines of Lake Malawi were free from schistosome, Schistosoma haematobium, transmission, but this changed in the mid-1980s, possibly as a result of over-fishing reducing density of molluscivore fishes. Very little information is available on schistosome infections among...

Reduction of allergenicity of irradiated ovalbumin in ovalbumin-allergic mice

International Nuclear Information System (INIS)

Seo, Ji-Hyun; Lee, Ju-Woon; Kim, Jae-Hun; Byun, Eui-Baek; Lee, Soo-Young; Kang, Il-Jun; Byun, Myung-Woo

2007-01-01

Egg allergy is one of the most serious of the immediate hypersensitivity reactions to foods. Such an allergic disorder is mediated by IgE antibodies stimulated by T-helper type 2 (Th2) lymphocytes. This study was undertaken to evaluate changes of allergenicity and cytokine profiles by exposure of irradiated ovalbumin (OVA), a major allergen of egg white, in the OVA-allergic mice model. OVA solutions (2 mg/ml in 0.01 M phosphate buffered saline (PBS) were gamma-irradiated to 50 and 100 kGy. The allergenicity in the OVA-allergy-induced mice model was remarkably reduced when challenged with irradiated OVA. Cultures of spleen cells harvested from OVA-sensitized mice showed a significant decrease in Th2 cytokine levels of ILs-4 and -5 with a concomitant increase in Th1 cytokine levels of IL-12 when co-cultured with irradiated OVA. However, IFN-γ level decreased dependant on the radiation dose of co-cultured OVA. The levels of IgEs and Th2-cytokine were reduced dependant on the radiation dose. These data show that the irradiated OVA could downregulate the activity of Th2 lymphocytes in OVA-sensitized mice

Allergen-Specific Immunotherapy with Monomeric Allergoid in a Mouse Model of Atopic Dermatitis

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Babakhin, Alexander; Andreev, Sergey; Nikonova, Alexandra; Shilovsky, Igor; Buzuk, Andrey; Elisyutina, Olga; Fedenko, Elena; Khaitov, Musa

2015-01-01

Atopic dermatitis (AD) is a widespread and difficult to treat allergic skin disease and is a tough challenge for healthcare. In this study, we investigated whether allergen-specific immunotherapy (ASIT) with a monomeric allergoid obtained by succinylation of ovalbumin (sOVA) is effective in a mouse model of atopic dermatitis. An experimental model of AD was reproduced by epicutaneous sensitization with ovalbumin (OVA). ASIT was performed with subcutaneous (SC) administration of increasing doses of OVA or sOVA. The levels of anti-OVA antibodies, as well as cytokines, were detected by ELISA. Skin samples from patch areas were taken for histologic examination. ASIT with either OVA or sOVA resulted in a reduction of both the anti-OVA IgE level and the IgG1/IgG2a ratio. Moreover, ASIT with sOVA increased the IFN-γ level in supernatants after splenocyte stimulation with OVA. Histologic analysis of skin samples from the sites of allergen application showed that ASIT improved the histologic picture by decreasing allergic inflammation in comparison with untreated mice. These data suggest that ASIT with a succinylated allergen represents promising approach for the treatment of AD. PMID:26275152

Systemic and Mucosal Antibody Responses to Soluble and Nanoparticle-Conjugated Antigens Administered Intranasally

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Savannah E. Howe

2016-10-01

Full Text Available Nanoparticles (NPs are increasingly being used for drug delivery, as well as antigen carriers and immunostimulants for the purpose of developing vaccines. In this work, we examined how intranasal (i.n. priming followed by i.n. or subcutaneous (s.c. boosting immunization affects the humoral immune response to chicken ovalbumin (Ova and Ova conjugated to 20 nm NPs (NP-Ova. We show that i.n. priming with 20 mg of soluble Ova, a dose known to trigger oral tolerance when administered via gastric gavage, induced substantial systemic IgG1 and IgG2c, as well as mucosal antibodies. These responses were further boosted following a s.c. immunization with Ova and complete Freund’s adjuvant (Ova+CFA. In contrast, 100 µg of Ova delivered via NPs induced an IgG1-dominated systemic response, and primed the intestinal mucosa for secretion of IgA. Following a secondary s.c. or i.n. immunization with Ova+CFA or NP-Ova, systemic IgG1 titers significantly increased, and serum IgG2c and intestinal antibodies were induced in mice primed nasally with NP-Ova. Only Ova- and NP-Ova-primed mice that were s.c.-boosted exhibited substantial systemic and mucosal titers for up to 6 months after priming, whereas the antibodies of i.n.-boosted mice declined over time. Our results indicate that although the amount of Ova delivered by NPs was 1000-fold less than Ova delivered in soluble form, the antigen-specific antibody responses, both systemic and mucosal, are essentially identical by 6 months following the initial priming immunization. Additionally, both i.n.- and s.c.-boosting strategies for NP-Ova-primed mice were capable of inducing a polarized Th1/Th2 immune response, as well as intestinal antibodies; however, it is only by using a heterogeneous prime-boost strategy that long-lasting antibody responses were initiated. These results provide valuable insight for future mucosal vaccine development, as well as furthering our understanding of mucosal antibody responses.

Bulinus nyassanus is an intermediate host for Schistosoma haematobium in Lake Malawi

DEFF Research Database (Denmark)

Madsen, H.; Bloch, P.; Phiri, H.

2001-01-01

At Cape Maclear on the Nankumba Peninsula, close to the southern end of Lake Malawi, Schistosoma haematobium is highly prevalent in the local people and many tourists become infected with this parasite each year. A 'Bilharzia Control Programme' was initiated in this area in August 1998......, field-collected B. nyassanus. These are remarkable observations since, although there are very few reports of diploid members of this species group being experimentally infected with S. haematobium, B. nyassanus is a diploid member (2n = 36) of the truncatus/tropicus group. Bulinus nyassanus is probably......, schistosome-infected B. nyassanus were discovered in surveys to identify transmission sites on the peninsula. Experimental infections of wild-caught B. nyassanus with S. haematobium proved successful and S. haematobium eggs were found in hamsters experimentally exposed to cercariae retrieved from schistosome-infected...

Spin-labelling study of interactions of ovalbumin with multilamellar liposomes and specific anti-ovalbumin antibodies.

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Brgles, Marija; Mirosavljević, Krunoslav; Noethig-Laslo, Vesna; Frkanec, Ruza; Tomasić, Jelka

2007-03-10

Ovalbumin (OVA) has been used continuously as the model antigen in numerous studies of immune reactions and antigen processing, very often encapsulated into liposomes. The purpose of this work was to study the possible interactions of spin-labelled OVA and lipids in liposomal membranes using electron spin resonance (ESR) spectroscopy. OVA was covalently spin-labelled with 4-maleimido-2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO-maleimide), characterized and encapsulated into multilamellar, negatively charged liposomes. ESR spectra of this liposomal preparation gave evidence for the interaction of OVA with the lipid bilayers. Such an interaction was also evidenced by the ESR spectra of liposomal preparation containing OVA, where liposomes were spin-labelled with n-doxyl stearic acids. The spin-labelled OVA retains its property to bind specific anti-OVA antibodies, as shown by ESR spectroscopy, but also in ELISA for specific anti-OVA IgG.

Feeding a Diet Enriched in Docosahexaenoic Acid to Lactating Dams Improves the Tolerance Response to Egg Protein in Suckled Pups

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Caroline Richard

2016-02-01

Full Text Available The objective of this study was to determine the effect of feeding a maternal diet supplemented with docosahexaenoic acid (DHA during the suckling period on the development of the immune system and oral tolerance (OT in offspring. Dams were randomized to consume one of two nutritionally adequate diets throughout the suckling period: control (N = 12, 0% DHA or DHA (N = 8, 0.9% DHA diet. At 11 days, pups from each dam were randomly assigned to a mucosal OT challenge: the placebo or the ovalbumin (OVA treatment. At three weeks, plasma immunoglobulins and splenocyte cytokine production ex vivo were measured. OVA-tolerized pups had a lower Th2 (IL-13 response to OVA despite the presence of more activated T cells and memory cells (CD27+, all p < 0.05. Feeding a high DHA diet improved the ability of splenocytes to respond to mitogens toward a skewed Th1 response and led to a higher IL-10 and a lower TGF-β production after stimulation with OVA (all p < 0.05. Untolerized DHA-fed pups had lower plasma concentrations of OVA-specific immunoglobulin E (p for interaction < 0.05. Overall, feeding a high DHA maternal diet improves the tolerance response in untolerized suckled pups in a direction that is thought to be beneficial for the establishment of OT.

Specific Schistosoma mansoni rat T cell clones. I. Generation and functional analysis in vitro and in vivo.

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Pestel, J; Dissous, C; Dessaint, J P; Louis, J; Engers, H; Capron, A

1985-06-01

In an attempt to determine the role of schistosome-specific T cells in the immune mechanisms developed during schistosomiasis, Schistosoma mansoni-specific T cells and clones were generated in vitro and some of their functions analyzed in vitro and in vivo in the fischer rat model. The data presented here can be summarized as follows: a) Lymph node cells (LNC) from rats primed with the excretory/secretory antigens-incubation products (IPSm) of adult worms proliferate in vitro only in response to the homologous schistosome antigens and not to unrelated antigens (Ag) such as ovalbumin (OVA) or Dipetalonema viteae and Fasciola hepatica parasite extracts. b) After in vitro restimulation of the primed LNC population with IPSm in the presence of antigen-presenting cells (APC) and maintenance in IL 2-containing medium, the frequency of IPSm-specific T cells is increased and the T cells can be restimulated only in the presence of APC possessing the same major histocompatibility complex (MHC) antigens. c) Following appropriate limiting dilution assays (LDA) (1 cell/well), 10 IPSm-specific T cell clones were obtained, and two of four maintained in culture were tested for their helper activity because they expressed only the W3/13+ W3/25+ surface phenotypes. d) The two highly proliferating IPSm-specific T cell clones (G5 and E23) exhibit an IPSm-dependent helper activity, as shown by the increase in IgG production by IPSm-primed B cells. e) IPSm-T cell clone (G5) as well as IPSm-T cell lines when injected in S. mansoni-infested rats can exert an in vivo helper activity, which is characterized by an accelerated production of IgG antibodies specific for the previously identified 30 to 40 kilodaltons (kd) schistosomula surface antigens (Ag). As recent studies have demonstrated that rat monoclonal antibodies recognize some incubation products of adult S. mansoni as well as one of the 30 to 40 kd schistosomula surface antigens, and taking into account the fact that the T cell

Combination immunotherapy with radiation and CpG-based tumor vaccination for the eradication of radio- and immuno-resistant lung carcinoma cells

International Nuclear Information System (INIS)

Chamoto, Kenji; Wakita, Daiko; Takeshima, Tsuguhide

2009-01-01

Unmethylated cytosine-phosphorothioate-guanine containing oligodeoxynucleotides (CpG-ODN) is known as a ligand of toll-like receptor 9 (TLR9), which selectively activates type-1 immunity. We have already reported that the vaccination of tumor-bearing mice with liposome-CpG coencapsulated with model-tumor antigen, ovalbumin (OVA) (CpG+OVA-liposome) caused complete cure of the mice bearing OVA-expressing EG-7 lymphoma cells. However, the same therapy was not effective to eradicate Lewis lung carcinoma (LLC)-OVA-carcinoma. To overcome the refractoriness of LLC-OVA, we tried the combination therapy of radiation with CpG-based tumor vaccination. When LLC-OVA-carcinoma intradermally (i.d.) injected into C57BL/6 became palpable (7-8 mm), the mice were irradiated twice with a dose of 14 Gy at intervals of 24 h. After the second radiation, CpG+OVA-liposome was i.d. administered near the draining lymph node (DLN) of the tumor mass. The tumor growth of mice treated with radiation plus CpG+OVA-liposome was greatly inhibited and approximately 60% of mice treated were completely cured. Moreover, the combined therapy with radiation and CpG+OVA-liposome allowed the augmented induction of OVA-tetramer + LLC-OVA-specific cytotoxic T lymphocyte (CTL) in DLN of tumor-bearing mice. These results indicate that the combined therapy of radiation with CpG-based tumor vaccine is a useful strategy to eradicate intractable carcinoma. (author)

Bladder cancer: Analysis of the 2004 WHO classification in ...

African Journals Online (AJOL)

Objectives: Bladder cancer (BCA) is aworldwide disease and shows a wide range of geographical variation. The aim of this study is to analyze the prevalence of schistosomal and non-schistosomal associated BCA as well as compare our findings with the 2004 WHO consensus classification of urothelial neoplasms and ...

Ovarian arteries supply to the pelvic lesions: angiographic identification and endovascular interventional management

International Nuclear Information System (INIS)

Wang Maoqiang; Liu Fengyong; Duan Feng; Wang Zhongpu; Wang Zhijun; Song Lei

2006-01-01

Objective: To investigate the frequency of the ovarian arteries (OVA) supply to the pelvic lesions and to evaluate the safety of transcatheter arterial embolization (TAE) of the OVA. Methods: Ninety-six patients referred for hypogastric-uterine arterial chemoembolization or embolization underwent selective ovarian arteriography,including pelvic malignancies in 63 cases, uterine fibroid in 17, and obstetric hemorrhage in 16 cases. Mean patient age was 46 years (range, 16-62 years). TAE supplementally was performed in patients with OVA supply to the pelvic lesions, using polyvinyl alcohol particles, gelatin sponge particles, and microcoils. The frequency of OVA supply to the pelvic lesions, the predictive factors, the technique and clinical significances of OVA embolization, were evaluated. Results: Bilateral OVA were catheterized selectively in 58 patients, and unilateral OVA in 38 patients. Thirty-three women (34.4%) had at least one ovarian artery supplying the pelvic lesions, including pelvic malignancies in 18, the fibroid in 5, and obstetric hemorrhage in 10 cases. The higher incidence of OVA supply to the pelvic lesions was observed in patients with obstetric disorders (χ 2 =6.73, P=0.009), with history of the pelvic surgery (χ 2 =3.55, P=0.04), with post embolization of the uterine arteries (χ 2 =6.80, P=0.009), and in patients with dysplasia of uterine artery bilaterally or unilaterally (χ 2 =3.40, P=0.04). Technical success of OVA embolization was achieved in the 33 cases, without severe complications related to the procedure. Persistent bleeding from the vagina was seen in 4 patients with obstetric hemorrhage after hypogastric-uterine arterial embolization, their bleeding ceased immediately after supplemental OVA embolization. Four patients developed transient symptoms of ovarian dysfunction after the hypogastric-uterine and OVA embolization. Conclusion: About 34% of the pelvic lesions can be supplied by OVA. Supplemental TAE of OVA is a safe and

Immunologic and metabolic effects of high-refined carbohydrate-containing diet in food allergic mice.

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Yamada, Letícia Tamie Paiva; de Oliveira, Marina Chaves; Batista, Nathália Vieira; Fonseca, Roberta Cristelli; Pereira, Rafaela Vaz Sousa; Perez, Denise Alves; Teixeira, Mauro Martins; Cara, Denise Carmona; Ferreira, Adaliene Versiani Matos

2016-02-01

Allergic mice show a reduction in body weight and adiposity with a higher inflammatory response in the adipose tissue similar to obese fat tissue. This study aimed to evaluate whether the low-grade inflammatory milieu of mice with diet-induced mild obesity interferes with the allergic response induced by ovalbumin (OVA). BALB/c mice were divided into four groups: 1) non-allergic (OVA-) mice fed chow diet, 2) allergic (OVA+) mice fed chow diet, 3) OVA- mice fed high-refined carbohydrate-containing (HC) diet, and 4) OVA+ mice fed HC diet. After 5 wk, allergic groups were sensitized with OVA and received a booster 14 d later. All groups received an oral OVA challenge 7 d after the booster. Allergic groups showed increased serum levels of total IgE, anti-OVA IgE, and IgG1; a high disease activity index score; aversion to OVA; and increased intestinal eosinophil infiltration. Non-allergic mild-obese mice also showed aversion to OVA and an increased number of eosinophils in the proximal jejunum. After the allergic challenge, OVA+ mice fed chow diet showed weight loss and lower adiposity in several adipose tissue depots. OVA+ mice fed HC diet showed a loss of fat mass only in the mesenteric adipose tissue. Furthermore, increased levels of TNF, IL-6, and IL-10 were observed in this tissue. Our data show that mild-obese allergic mice do not present severe pathologic features of food allergy similar to those exhibited by lean allergic mice. Mild obesity promoted by HC diet ingestion causes important intestinal disorders that appear to modulate the inflammatory response during the antigen challenge. Copyright © 2016 Elsevier Inc. All rights reserved.

A phosphatidylinositol 3-kinase inhibitor strongly suppressed pulmonary vascular remodeling of allergic vasculitis in a murine model.

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Oikawa, Yuka; Sasaki, Nobuhito; Niisato, Miyuki; Nakamura, Yutaka; Yamauchi, Kohei

2016-04-01

We investigated the effects of pan-class I PI3K inhibitor, ZSTK474 on vascular remodeling using a murine model of allergic vasculitis with eosinophil infiltration. C57BL/6 mice were sensitized with OVA. The positive controls were exposed to aerosolized OVA daily for 7 days. The other group of mice were administered ZSTK474 (30 mg/kg, p.o. daily) in parallel with daily exposure to aerosolized OVA for 7 days. On the 3rd and 7th day, bronchoalveolar lavage (BAL) was performed and the lungs were excised for pathological analysis. Cell differentials were determined and the concentrations of IL-4, IL-5, IL-13 and TGF-βin BAL fluid were measured. The total cell numbers and eosinophil numbers in BALF were greatly reduced in the ZSTK474-treated group on the 3rd and 7th day after exposure to OVA. The numbers of total white blood cells and eosinophils in the peripheral blood were significantly reduced in the ZSTK474-treated group on the 3rd and 7th day after exposure to OVA. The concentrations of IL-4, IL-5, and IL-13 in BAL fluids were also reduced significantly on the 3rd day in the ZSTK474-treated group. The concentrations of TGF-β in BAL fluids were also reduced significantly on the 3rd and 7th day in the ZSTK474-treated group. The pathological scores reduced significantly in the ZSTK474-treated group compared to the control group. The PI3K inhibitor, ZSTK474 suppressed pulmonary vascular remodeling in the murine model of allergic vasculitis with eosinophil infiltration. PI3K signal transduction may have a critical role in the immunological process that induces allergic vasculitis.

Improving release completeness from PLGA-based implants for the acid-labile model protein ovalbumin.

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Duque, Luisa; Körber, Martin; Bodmeier, Roland

2018-03-01

The objectives of this study were to assess the feasibility of hot melt extrusion (HME) for the preparation of PLGA-based ovalbumin-loaded implants as well as to characterize and improve protein release from the implants. Ovalbumin (OVA) was stable during extrusion, which was attributed to a protective effect of the biodegradable matrix. OVA release was characterized by a low burst, a slow release up to day 21, which plateaued thereafter resulting in incomplete release for all evaluated protein loadings. Release incompleteness was accompanied by the formation of an insoluble residual mass. Further characterization of this mass indicated that it consisted of non-covalent protein aggregates and polymer, where ovalbumin was ionically bound as the pH inside the degrading matrix decreased below the pI of the protein. Although higher protein release was obtained with the inclusion of weak bases because of their neutralizing effect, OVA aggregation and release incompleteness were not fully avoided. With the use of shellac, a well-known enteric and biocompatible polymer, as protective excipient, a distinct late release phase occurred and release completeness was increased to more than 75% cumulative release. Shellac apparently protected the protein against the acidic microclimate due to its low solubility at low pH. Protected OVA was thus released once the pH increased due to a declining PLGA-oligomer formation. The result was a triphasic release profile consisting of an initial burst, a slow diffusion phase over about 7 weeks, and an erosion-controlled dissolution phase over the next 3 weeks. An acid-labile protein like OVA was thus feasibly protected from interactions with PLGA and its degradation products, resulting in a controlled delivery of more than 85% of the original payload. Copyright © 2018 Elsevier B.V. All rights reserved.

Identification and characterization of novel microRNAs from Schistosoma japonicum.

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Xiangyang Xue

Full Text Available BACKGROUND: Schistosomiasis japonica remains a major public health problem in China. Its pathogen, Schistosoma japonicum has a complex life cycle and a unique repertoire of genes expressed at different life cycle stages. Exploring schistosome gene regulation will yield the best prospects for new drug targets and vaccine candidates. MicroRNAs (miRNAs are a highly conserved class of noncoding RNA that control many biological processes by sequence-specific inhibition of gene expression. Although a large number of miRNAs have been identified from plants to mammals, it remains no experimental proof whether schistosome exist miRNAs. METHODOLOGY AND RESULTS: We have identified novel miRNAs from Schistosoma japonicum by cloning and sequencing a small (18-26 nt RNA cDNA library from the adult worms. Five novel miRNAs were identified from 227 cloned RNA sequences and verified by Northern blot. Alignments of the miRNAs with corresponding family members indicated that four of them belong to a metazoan miRNA family: let-7, miR-71, bantam and miR-125. The fifth potentially new (non conserved miRNA appears to belong to a previously undescribed family in the genus Schistosome. The novel miRNAs were designated as sja-let-7, sja-miR-71, sja-bantam, sja-miR-125 and sja-miR-new1, respectively. Expression of sja-let-7, sja-miR-71 and sja-bantam were analyzed in six stages of the life cycle, i.e. egg, miracidium, sporocyst, cercaria, schistosomulum, and adult worm, by a modified stem-loop reverse transcribed polymerase chain reaction (RT-PCR method developed in our laboratory. The expression patterns of these miRNAs were highly stage-specific. In particular, sja-miR-71 and sja-bantam expression reach their peaks in the cercaria stage and then drop quickly to the nadirs in the schistosomulum stage, following penetration of cercaria into a mammalian host. CONCLUSIONS: Authentic miRNAs were identified for the first time in S. japonicum, including a new schistosome

Natural Killer Receptor 1 Dampens the Development of Allergic Eosinophilic Airway Inflammation.

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Shirin Elhaik Goldman

Full Text Available The function of NCR1 was studied in a model of experimental asthma, classified as a type 1 hypersensitivity reaction, in mice. IgE levels were significantly increased in the serum of OVA immunized NCR1 deficient (NCR1gfp/gfp mice in comparison to OVA immunized wild type (NCR1+/+ and adjuvant immunized mice. Histological analysis of OVA immunized NCR1gfp/gfp mice revealed no preservation of the lung structure and overwhelming peribronchial and perivascular granulocytes together with mononuclear cells infiltration. OVA immunized NCR+/+ mice demonstrated preserved lung structure and peribronchial and perivascular immune cell infiltration to a lower extent than that in NCR1gfp/gfp mice. Adjuvant immunized mice demonstrated lung structure preservation and no immune cell infiltration. OVA immunization caused an increase in PAS production independently of NCR1 presence. Bronchoalveolar lavage (BAL revealed NCR1 dependent decreased percentages of eosinophils and increased percentages of lymphocytes and macrophages following OVA immunization. In the OVA immunized NCR1gfp/gfp mice the protein levels of eosinophils' (CCL24 and Th2 CD4+ T-cells' chemoattractants (CCL17, and CCL24 in the BAL are increased in comparison with OVA immunized NCR+/+ mice. In the presence of NCR1, OVA immunization caused an increase in NK cells numbers and decreased NCR1 ligand expression on CD11c+GR1+ cells and decreased NCR1 mRNA expression in the BAL. OVA immunization resulted in significantly increased IL-13, IL-4 and CCL17 mRNA expression in NCR1+/+ and NCR1gfp/gfp mice. IL-17 and TNFα expression increased only in OVA-immunized NCR1+/+mice. IL-6 mRNA increased only in OVA immunized NCR1gfp/gfp mice. Collectively, it is demonstrated that NCR1 dampens allergic eosinophilic airway inflammation.

Oral tolerance induction with altered forms of ovalbumin

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Stransky B.

1998-01-01

Full Text Available As a T cell-dependent phenomenon, oral tolerance is not expected to depend necessarily on native configuration of antigens. We investigated the induction of oral tolerance with modified ovalbumin (Ova. Oral administration of heat-denatured (HD-Ova and cyanogen bromide-degraded ovalbumin was less effective than native Ova in inducing oral tolerance in B6D2F1 mice. HD-Ova was effective in suppressing delayed-type hypersensitivity (DTH reactions but did not suppress specific antibody formation. Injection of Ova directly into the stomach, but not into the ileum or cecum, suppressed subsequent immunization to DTH reactions. Gavage with protease inhibitors (aprotinin or ovomucoid before gavage with Ova was ineffective in blocking tolerance induction. Treatment with hydroxyurea to destroy cycling cells 24 h before gavage with Ova blocked oral tolerance induction and also the possibility to passively transfer tolerance to naive recipients with the serum of mice gavaged with Ova 1 h before. The implications of these findings about oral tolerance induction are discussed

Aluminium per se and in the anti-acid drug sucralfate promotes sensitization via the oral route.

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Brunner, R; Wallmann, J; Szalai, K; Karagiannis, P; Altmeppen, H; Riemer, A B; Jensen-Jarolim, E; Pali-Schöll, I

2009-06-01

Aluminium (ALUM) is used as experimental and clinical adjuvant for parenteral vaccine formulation. It is also contained in anti-acid drugs like sucralfate (SUC). These anti-acids have been shown to cause sensitization to food proteins via elevation of the gastric pH. The aim of this study was to assess the oral adjuvant properties of ALUM, alone or contained in SUC, in a BALB/c mouse model. Mice were fed SUC plus ovalbumin (OVA) and compared with groups where ALUM or proton pump inhibitors (PPI) were applied as adjuvants. The humoral and cellular immune responses were assessed on antigen-specific antibody and cytokine levels. The in vivo relevance was investigated in skin tests. The highest OVA-specific immunoglobulin G1 (IgG1) and IgE antibody levels were found in mice fed with OVA/SUC, followed by OVA/ALUM-treated animals, indicating a T helper 2 (Th2) shift in both groups. Antibody levels in other groups revealed lower (OVA/PPI-group) or baseline levels (control groups). Positive skin tests confirmed an allergic response in anti-acid or adjuvant-treated animals. Our data show for the first time that ALUM acts as a Th2-adjuvant via the oral route. This suggests that orally applied SUC leads to an enhanced risk for food allergy, not only by inhibiting peptic digestion but also by acting as a Th2-adjuvant by its ALUM content.

Breast regression protein-39 (BRP-39) promotes dendritic cell maturation in vitro and enhances Th2 inflammation in murine model of asthma.

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Xu, Qian; Chai, Shou-jie; Qian, Ying-ying; Zhang, Min; Wang, Kai

2012-12-01

To determine the roles of breast regression protein-39 (BRP-39) in regulating dendritic cell maturation and in pathology of acute asthma. Mouse bone marrow-derived dendritic cells (BMDCs) were prepared, and infected with adenovirus over-expressing BRP-39. Ovalbumin (OVA)-induced murine model of acute asthma was made in female BALB/c mice by sensitizing and challenging with chicken OVA and Imject Alum. The transfected BMDCs were adoptively transferred into OVA-treated mice via intravenous injection. Airway hyperresponsiveness (AHR), inflammation and pulmonary histopathology were characterized. The expression of BRP-39 mRNA and protein was significantly increased in lung tissues of OVA-treated mice. The BMDCs infected with adenovirus BRP-39 exhibited greater maturation and higher activity in vitro. Adoptive transfer of the cells into OVA-treated mice significantly augmented OVA-induced AHR and eosinophilic inflammation. Meanwhile, BRP-39 further enhanced the production of OVA-induced Th2 cytokines IL-4, IL-5 and IL-13, but significantly attenuated OVA-induced IFN-γ production in bronchoalveolar lavage fluid. In OVA-induced murine model of acute asthma, BRP-39 is over-expressed in lung tissue and augments Th2 inflammatory response and AHR. BRP-39 promotes dendritic cell maturation in vitro. Therefore, BRP-39 may be a potential therapeutic target of asthma.

Chitinase 3-like 1 protein levels are elevated in Schistosoma haematobium infected children.

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Laura J Appleby

Full Text Available Currently there are few studies characterising the nature and aetiology of human schistosome-related inflammatory processes. The aim of this study was to determine the relationship between Chitinase 3-like 1 (CHI3L1, also known as YKL-40, a molecule associated with inflammatory processes, and schistosome infection, morbidity and systemic cytokine levels.Serological levels of CHI3L1 and a panel of cytokines (IFN-y, IL-4/5/6/9/10/13 and 17 were measured in two Zimbabwean populations resident in a high and low schistosome infection area. CHI3L1 levels were related to schistosome infection, haematuria status and cytokine levels after allowing for confounding variables. The effect of antihelminthic treatment with praziquantel on CHI3L1 levels was determined in 246 participants 6 weeks post-treatment.CHI3L1 levels increased with age in both areas but were significantly higher in the high infection areas compared to the low infection area. CHI3L1 levels were also higher in infected compared to uninfected individuals with this difference being significant in the youngest age group. Curative antihelminthic treatment resulted in a significant decrease in CHI3L1 levels. Of the cytokines, only IL-10 and IL-17 had a significant association with CHI3L1 levels, and this association was negative.Serum CHI3L1 levels differ between infected and uninfected people before and after antihelminthic treatment. The greatest difference occurs in the youngest age group, in keeping with the period when schistosome-related pathological processes are initiated. Following from previous studies in non-infectious diseases showing that CHI3L1 is a biomarker for the inflammatory process, this study suggests that the potential for CHI3L1 as a biomarker for schistosome-related pathology should be explored further.

Allergy adjuvant effect of particles from wood smoke and road traffic.

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Samuelsen, Mari; Nygaard, Unni Cecilie; Løvik, Martinus

2008-04-18

There is growing evidence that in addition to augmenting the severity of asthma and allergic diseases, particulate air pollution also increases the incidence of allergy and asthma. We studied the adjuvant effect of particles from wood smoke and road traffic on the immune response to the allergen ovalbumin (OVA). OVA with and without particles was injected into one hind footpad of Balb/cA mice. All particles together with OVA significantly increased the level of OVA-specific immunoglobulin E (IgE) in serum, compared to groups given OVA or particles alone. Reference diesel exhaust particles (DEP) with OVA induced the highest levels of IgE, whereas no clear difference was observed between particles from road traffic and wood smoke. Road traffic particles collected in the autumn induced higher IgE values with OVA than corresponding particles collected during the winter season when studded tires are used, suggesting that studded tire-generated road pavement particles have less allergy adjuvant activity than exhaust particles. Compared to OVA or particles alone, all particles with OVA increased popliteal lymph node cell numbers, cell proliferation, ex vivo secretion of IL-4 and IL-10 after ConA stimulation, and the expression of several cell surface molecules (CD19, MHC class II, CD86 and CD23). Wood smoke particles with OVA induced somewhat higher cellular responses than road traffic particles, but less than DEP with OVA which seemed to be the most potent particle in inducing cellular as well as antibody responses. Thus, wood smoke particles had about the same capacity to enhance allergic sensitization as road traffic particles, but less than diesel exhaust particles.

Allergy adjuvant effect of particles from wood smoke and road traffic

International Nuclear Information System (INIS)

Samuelsen, Mari; Nygaard, Unni Cecilie; Lovik, Martinus

2008-01-01

There is growing evidence that in addition to augmenting the severity of asthma and allergic diseases, particulate air pollution also increases the incidence of allergy and asthma. We studied the adjuvant effect of particles from wood smoke and road traffic on the immune response to the allergen ovalbumin (OVA). OVA with and without particles was injected into one hind footpad of Balb/cA mice. All particles together with OVA significantly increased the level of OVA-specific immunoglobulin E (IgE) in serum, compared to groups given OVA or particles alone. Reference diesel exhaust particles (DEP) with OVA induced the highest levels of IgE, whereas no clear difference was observed between particles from road traffic and wood smoke. Road traffic particles collected in the autumn induced higher IgE values with OVA than corresponding particles collected during the winter season when studded tires are used, suggesting that studded tire-generated road pavement particles have less allergy adjuvant activity than exhaust particles. Compared to OVA or particles alone, all particles with OVA increased popliteal lymph node cell numbers, cell proliferation, ex vivo secretion of IL-4 and IL-10 after ConA stimulation, and the expression of several cell surface molecules (CD19, MHC class II, CD86 and CD23). Wood smoke particles with OVA induced somewhat higher cellular responses than road traffic particles, but less than DEP with OVA which seemed to be the most potent particle in inducing cellular as well as antibody responses. Thus, wood smoke particles had about the same capacity to enhance allergic sensitization as road traffic particles, but less than diesel exhaust particles

Seasonal dynamics of snail populations in coastal Kenya: Model calibration and snail control

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Gurarie, D.; King, C. H.; Yoon, N.; Wang, X.; Alsallaq, R.

2017-10-01

A proper snail population model is important for accurately predicting Schistosoma transmission. Field data shows that the overall snail population and that of shedding snails have a strong pattern of seasonal variation. Because human hosts are infected by the cercariae released from shedding snails, the abundance of the snail population sets ultimate limits on human infection. For developing a predictive dynamic model of schistosome infection and control strategies we need realistic snail population dynamics. Here we propose two such models based on underlying environmental factors and snail population biology. The models consist of two-stage (young-adult) populations with resource-dependent reproduction, survival, maturation. The key input in the system is seasonal rainfall which creates snail habitats and resources (small vegetation). The models were tested, calibrated and validated using dataset collected in Msambweni (coastal Kenya). Seasonal rainfall in Msambweni is highly variable with intermittent wet - dry seasons. Typical snail patterns follow precipitation peaks with 2-4-month time-lag. Our models are able to reproduce such seasonal variability over extended period of time (3-year study). We applied them to explore the optimal seasonal timing for implementing snail control.

Peptide-loaded dendritic cells prime and activate MHC-class I-restricted T cells more efficiently than protein-loaded cross-presenting DC

DEFF Research Database (Denmark)

Met, Ozcan; Buus, Søren; Claesson, Mogens H

2003-01-01

-pulsed DC. Moreover, SIINFEKL-loaded DC were up to 50 times more efficient than DC-pulsed with OVA-protein for generation of an H-2K(b)-restricted response. Immunization of mice with SIINFEKL-loaded DC resulted in a much stronger H-2K(b)-restricted response than immunization with OVA-pulsed DC. These data......Undifferentiated and differentiated dendritic cells (uDC and dDC, respectively), derived from the bone marrow, were studied in vitro and in vivo. Ovalbumin (OVA) and two OVA-derived peptides binding to H-2K(b) and I-A(b), respectively, were used. Two IL-2 secreting T cell hybridomas specific...... for the OVA-derived epitopes were used in the in vitro read-out. The ability to cross-present the H-2K(b) binding OVA(257-264)-peptide (SIINFEKL) was restricted to dDC, which express CD11c(+), CD86(+), and MHC-II(+). In vitro, the antigenicity of SIINFEKL-loaded DC declined at a slower rate than that of OVA...

Oral Gene Application Using Chitosan-DNA Nanoparticles Induces Transferable Tolerance

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Ensminger, Stephan M.; Spriewald, Bernd M.

2012-01-01

Oral tolerance is a promising approach to induce unresponsiveness to various antigens. The development of tolerogenic vaccines could be exploited in modulating the immune response in autoimmune disease and allograft rejection. In this study, we investigated a nonviral gene transfer strategy for inducing oral tolerance via antigen-encoding chitosan-DNA nanoparticles (NP). Oral application of ovalbumin (OVA)-encoding chitosan-DNA NP (OVA-NP) suppressed the OVA-specific delayed-type hypersensitivity (DTH) response and anti-OVA antibody formation, as well as spleen cell proliferation following OVA stimulation. Cytokine expression patterns following OVA stimulation in vitro showed a shift from a Th1 toward a Th2/Th3 response. The OVA-NP-induced tolerance was transferable from donor to naïve recipient mice via adoptive spleen cell transfer and was mediated by CD4+CD25+ T cells. These findings indicate that nonviral oral gene transfer can induce regulatory T cells for antigen-specific immune modulation. PMID:22933401

Viability of developmental stages of Schistosoma mansoni quantified with xCELLigence worm real-time motility assay (xWORM

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Gabriel Rinaldi

2015-12-01

Full Text Available Infection with helminth parasites causes morbidity and mortality in billions of people and livestock worldwide. Where anthelmintic drugs are available, drug resistance is a major problem in livestock parasites, and a looming threat to public health. Monitoring the efficacy of these medicines and screening for new drugs has been hindered by the lack of objective, high-throughput approaches. Several cell monitoring technologies have been adapted for parasitic worms, including video-, fluorescence-, metabolism enzyme- and impedance-based tools that minimize the screening bottleneck. Using the xCELLigence impedance-based system we previously developed a motility-viability assay that is applicable for a range of helminth parasites. Here we have improved substantially the assay by using diverse frequency settings, and have named it the xCELLigence worm real-time motility assay (xWORM. By utilizing strictly standardized mean difference analysis we compared the xWORM output measured with 10, 25 and 50 kHz frequencies to quantify the motility of schistosome adults (human blood flukes and hatching of schistosome eggs. Furthermore, we have described a novel application of xWORM to monitor movement of schistosome cercariae, the developmental stage that is infectious to humans. For all three stages, 25 kHz was either optimal or near-optimal for monitoring and quantifying schistosome motility. These improvements in methodology sensitivity should enhance the capacity to screen small compound libraries for new drugs both for schistosomes and other helminth pathogens at large.

Early Oral Ovalbumin Exposure during Maternal Milk Feeding Prevents Spontaneous Allergic Sensitization in Allergy-Prone Rat Pups

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Adaweyah El-Merhibi

2012-01-01

Full Text Available There are conflicting data to support the practice of delaying the introduction of allergenic foods into the infant diet to prevent allergy development. This study investigated immune response development after early oral egg antigen (Ovalbumin; OVA exposure in a rat pup model. Brown Norway (BN rat pups were randomly allocated into groups: dam reared (DR, DR pups challenged daily (days 4–13 with oral OVA (DR + OVAc, DR pups challenged intermittently (on day 4, 10, 12, and 13 with oral OVA (DR + OVAi, formula-fed pups (FF, and FF pups challenged daily with oral OVA (FF + OVA. Immune parameters assessed included OVA-specific serum IgE, IgG1, and IgA. Ileal and splenic messenger ribonucleic acid (mRNA expression of transforming growth factor-beta (TGF-β1, mothers against decapentaplegic (Smad 2/4/7, and forkhead box P3 (Foxp3 were determined. Ileum was stained for TGF-β1 and Smad4. Results. Feeding OVA daily to DR pups maintained systemic and local gut antibody and immunoregulatory marker mRNA responses. Systemic TGF-β1 was lower in DR + OVAi pups compared to DR and DR + OVAc pups. Feeding OVA to FF pups resulted in significantly greater OVA-specific IgE and IgG1, and lower IgA and TGF-β1 and Smad expression compared to DR pups. Conclusions. Early daily OVA exposure in the presence of maternal milk maintains immune markers associated with a regulated immune response, preventing early allergic sensitization.

Antigen delivery by α2-macroglobulin enhances the cytotoxic T lymphocyte response

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Bowers, Edith V.; Horvath, Jeffrey J.; Bond, Jennifer E.; Cianciolo, George J.; Pizzo, Salvatore V.

2009-01-01

α2M* targets antigens to APCs for rapid internalization, processing, and presentation. When used as an antigen-delivery vehicle, α2M* amplifies MHC class II presentation, as demonstrated by increased antibody titers. Recent evidence, however, suggests that α2M* encapsulation may also enhance antigen-specific CTL immunity. In this study, we demonstrate that α2M*-delivered antigen (OVA) enhances the production of specific in vitro and in vivo CTL responses. Murine splenocytes expressing a transgenic TCR specific for CTL peptide OVA257–264 (SIINFEKL) demonstrated up to 25-fold greater IFN-γ and IL-2 secretion when treated in vitro with α2M*-OVA compared with soluble OVA. The frequency of IFN-γ-producing cells was increased ∼15-fold, as measured by ELISPOT. Expansion of the OVA-specific CD8+ T cell population, as assayed by tetramer binding and [3H]thymidine incorporation, and OVA-specific cell-mediated cytotoxicity, as determined by a flow cytometric assay, were also enhanced significantly by α2M*-OVA. Furthermore, significant CTL responses were observed at antigen doses tenfold lower than those required with OVA alone. Finally, we also observed enhanced humoral and CTL responses by naïve mice following intradermal immunization with α2M*-OVA. These α2M*-OVA-immunized mice demonstrated increased protection against a s.c.-implanted, OVA-expressing tumor, as demonstrated by delayed tumor growth and prolonged animal survival. The observation that α2M*-mediated antigen delivery elicits specific CTL responses suggests the cross-presentation of antigen onto MHC class I. These results support α2M* as an effective antigen-delivery system that may be particularly useful for vaccines based on weakly immunogenic subunits or requiring dose sparing. PMID:19652028

Maternal allergen immunisation to prevent sensitisation in offspring: Th2-polarising adjuvants are more efficient than a Th1-polarising adjuvant in mice

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Melkild Ingrid

2010-03-01

Full Text Available Abstract Background Allergy has been an increasing problem in several parts of the world. Prenatal exposure to allergen and microbial components may affect the development of allergies in childhood, as indicated by epidemiological and experimental studies. We investigated the capacity for allergic sensitisation in offspring after induction of a Th1- or a Th2-polarised immune response to the same allergen in mothers during pregnancy. Results During pregnancy, mice were immunised with ovalbumin (OVA given with either one of the Th2-adjuvants pertussis toxin (PT or Al(OH3 (aluminium hydroxide, or with the Th1 adjuvant CpG. Offspring were immunised with OVA in Al(OH3 as young adults. Serum and supernatants from ex vivo stimulated or non-stimulated spleen cells from mothers and offspring were analysed for OVA-specific antibodies and cytokines, respectively. Mothers immunised with OVA together with either Al(OH3 or PT had increased levels of OVA-specific IgE and IgG1 compared to naive mothers, whereas mothers immunised with OVA together with CpG had increased levels of OVA-specific IgG2a compared to naive mothers. In general the highest levels of IL-5, IL-10, and IFNγ were observed in spleen cells from mothers immunised with PT and OVA. Upon immunisation, offspring from mothers immunised with OVA and either PT or Al(OH3 showed reduced levels of OVA-specific IgE and IgG1 and increased levels of OVA-specific IgG2a antibodies compared to offspring from naive mothers. Maternal immunisation with CpG and OVA did not affect antibody responses in offspring. Conclusion Allergic sensitisation in the offspring was affected by the type of adjuvant used for immunisation of the mothers with the same allergen. Th2 polarisation of the immune response in the mothers was found to give reduced IgE levels upon sensitisation of the offspring, whereas no reduction was achieved with Th1 polarisation in the mothers.

Development of nanoparticle based delivery systems for sublingual immunotherapy

DEFF Research Database (Denmark)

Alija, Hava; Rask, Carola; Brimnes, Jens

The prevalence of IgE mediated allergic diseases is increasing dramatically in industrialized countries. Sublingual immunotherapy (SLIT) has been demonstrated to be a safe and efficacious treatment for IgE mediated allergic diseases, but requires protracted treatment duration. Even though SLIT...... (OVA)-induced allergic airway inflammation model for their ability to improve immune tolerance induction of ovalbumin (protein and peptide) when delivered sublingually. In the liposome study, mice were treated sublingually during two weeks with free or liposome encapsulated OVA (OVA-liposomes) followed...... by intraperitoneal injections and intranasal challenge. Mice treated sublingually with OVA-liposomes showed a significant reduction of airway eosinophilia, OVA-specific IgE antibodies and splenocyte proliferation in comparison to free OVA. In addition, reduced levels of IFN-ɣ and IL-5 were observed in spleen cell...

Role of Regulatory Immune Responses in the Pathogenesis of Schistosomiasis

Science.gov (United States)

2008-07-15

world’s population, suffer from helminth (worm) infections (Colley et al., 2001). Schistosomiasis, a helminth infection caused by trematode parasites of...roughly one tenth of all helminth infections (Organization, 1993). Similar to other parasites , schistosomes have evolved mechanisms to evade...the TGF- -like receptor/Smad signaling pathway in parasitic helminths themselves has been shown to be important in regulating schistosome

Transgene IL-6 Enhances DC-Stimulated CTL Responses by Counteracting CD4+25+Foxp3+ Regulatory T Cell Suppression via IL-6-Induced Foxp3 Downregulation

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Kalpana Kalyanasundaram Bhanumathy

2014-03-01

Full Text Available Dendritic cells (DCs, the most potent antigen-presenting cells have been extensively applied in clinical trials for evaluation of antitumor immunity. However, the efficacy of DC-mediated cancer vaccines is still limited as they are unable to sufficiently break the immune tolerance. In this study, we constructed a recombinant adenoviral vector (AdVIL-6 expressing IL-6, and generated IL-6 transgene-engineered DC vaccine (DCOVA/IL-6 by transfection of murine bone marrow-derived ovalbumin (OVA-pulsed DCs (DCOVA with AdVIL-6. We then assessed DCOVA/IL-6-stimulated cytotoxic T-lymphocyte (CTL responses and antitumor immunity in OVA-specific animal tumor model. We demonstrate that DCOVA/IL-6 vaccine up-regulates expression of DC maturation markers, secretes transgene-encoded IL-6, and more efficiently stimulates OVA-specific CTL responses and therapeutic immunity against OVA-expressing B16 melanoma BL6-10OVA in vivo than the control DCOVA/Null vaccine. Moreover, DCOVA/IL-6-stimulated CTL responses were relatively maintained in mice with transfer of CD4+25+Foxp3+ Tr-cells, but significantly reduced when treated with anti-IL-6 antibody. In addition, we demonstrate that IL-6 down-regulates Foxp3-expression of CD4+25+Foxp3+ Tr-cells in vitro. Taken together, our results demonstrate that AdV-mediated IL-6 transgene-engineered DC vaccine stimulates potent CTL responses and antitumor immunity by counteracting CD4+25+ Tr immunosuppression via IL-6-induced Foxp3 down-regulation. Thus, IL-6 may be a good candidate for engineering DCs for cancer immunotherapy.

Dimethyl sulfoxide in a 10% concentration has no effect on oxidation stress induced by ovalbumin-sensitization in a guinea-pig model of allergic asthma.

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Mikolka, P; Mokra, D; Drgova, A; Petras, M; Mokry, J

2012-04-01

In allergic asthma, activated cells produce various substances including reactive oxygen species (ROS). As heterogenic pathophysiology of asthma results to different response to the therapy, testing novel interventions continues. Because of water-insolubility of some potentially beneficial drugs, dimethyl sulfoxide (DMSO) is often used as a solvent. Based on its antioxidant properties, this study evaluated effects of DMSO on mobilization of leukocytes into the lungs, and oxidation processes induced by ovalbumin (OVA)-sensitization in a guinea-pig model of allergic asthma. Guinea-pigs were divided into OVA-sensitized and naive animals. One group of OVA-sensitized animals and one group of naive animals were pretreated with 10% DMSO, the other two groups were given saline. After sacrificing animals, blood samples were taken and total antioxidant status (TAS) in the plasma was determined. Left lungs were saline-lavaged and differential leukocyte count in bronchoalveolar lavage fluid (BAL) was made. Right lung tissue was homogenized, TAS and products of lipid and protein oxidation were determined in the lung homogenate and in isolated mitochondria. OVA-sensitization increased total number of cells and percentages of eosinophils and neutrophils in BAL fluid; increased lipid and protein oxidation in the lung homogenate and mitochondria, and decreased TAS in the lungs and plasma compared with naive animals. However, no differences were observed in DMSO-instilled animals compared to controls. In conclusion, OVA-sensitization increased mobilization of leukocytes into the lungs and elevated production of ROS, accompanied by decrease in TAS. 10% DMSO had no effect on lipid and protein oxidation in a guinea-pig model of allergic asthma.

Long-term reduction in food allergy susceptibility in mice by combining breastfeeding-induced tolerance and TGF-β-enriched formula after weaning.

Science.gov (United States)

Rekima, A; Macchiaverni, P; Turfkruyer, M; Holvoet, S; Dupuis, L; Baiz, N; Annesi-Maesano, I; Mercenier, A; Nutten, S; Verhasselt, V

2017-04-01

Oral tolerance induction in early life is a promising approach for food allergy prevention. Its success requires the identification of factors necessary for its persistence. We aimed to assess in mice duration of allergy prevention by breastfeeding-induced oral tolerance and whether oral TGF-β supplementation after weaning would prolong it. We quantified ovalbumin (OVA) and OVA-specific immunoglobulin levels by ELISA in milk from the EDEN birth cohort. As OVA-specific Ig was found in all samples, we assessed whether OVA-immunized mice exposed to OVA during lactation could prevent allergic diarrhoea in their 6- and 13-week-old progeny. In some experiments, a TGF-β-enriched formula was given after weaning. At 6 weeks, only 13% and 34% of mice breastfed by OVA-exposed mothers exhibited diarrhoea after six and seven OVA challenges vs. 44% and 72% in mice breastfed by naïve mothers (P = 0.02 and 0.01). Protection was associated with decreased levels of MMCP1 and OVA-specific IgE (P food allergy by breastfeeding-induced tolerance is of limited duration. Nutritional intervention by TGF-β supplementation after weaning could prolong beneficial effects of breast milk on food allergy prevention. © 2016 John Wiley & Sons Ltd.

Combined effect of glycation and sodium carbonate-bicarbonate buffer concentration on IgG binding, IgE binding and conformation of ovalbumin.

Science.gov (United States)

Ma, Xiao-juan; Gao, Jin-yan; Chen, Hong-bing

2013-10-01

Ovalbumin (OVA) is a major allergen in hen egg. During thermal processing, reducing sugars contained in the hen egg white might easily undergo glycation with OVA, but few studies have been conducted on its corresponding immunoreactivity changes. The aim of the present study was to assess changes of the antigenicity, potential allergenicity and conformation of OVA after glycation in a wet-thermal processing system under different concentrations of sodium carbonate-bicarbonate buffer. IgE binding of the glycated OVA was increased after glycation, and the higher the sodium carbonate-bicarbonate buffer concentration, the higher the IgE binding capacity. The increase in IgE binding of OVA corresponded well with the disruption of the disulfide bond, which exposed the epitopes initially buried. Antigenicity of the glycated OVA was increased, and the amount of the increase varied among samples treated under different buffer concentrations. Glycation increased the allergenic potential for OVA, with the amount of increase varying with different sodium carbonate-bicarbonate buffer concentrations. © 2013 Society of Chemical Industry.

Acute airway effects of airborne formaldehyde in sensitized and non-sensitized mice housed in a dry or humid environment

Energy Technology Data Exchange (ETDEWEB)

Larsen, Søren Thor, E-mail: stl@nrcwe.dk; Wolkoff, Peder, E-mail: pwo@nrcwe.dk; Hammer, Maria, E-mail: mha@nrcwe.dk; Kofoed-Sørensen, Vivi, E-mail: vks@nrcwe.dk; Clausen, Per Axel, E-mail: pac@nrcwe.dk; Nielsen, Gunnar Damgård, E-mail: gdn@nrcwe.dk

2013-05-01

We investigated the role of air humidity and allergic sensitization on the acute airway response to inhaled formaldehyde (FA) vapor. Mice were sensitized to the immunogen ovalbumin (OVA) by three intraperitoneal injections followed by two aerosol challenges, giving rise to allergic airway inflammation. Control mice were sham sensitized by saline injections and challenged by saline aerosols. Once sensitized, the mice were housed at high (85–89%) or low (< 10%) relative humidity, respectively for 48 h prior to a 60-min exposure to either 0.4, 1.8 or about 5 ppm FA. Before, during and after exposure, breathing parameters were monitored. These included the specific markers of nose and lung irritations as well as the expiratory flow rate, the latter being a marker of airflow limitation. The sensory irritation response in the upper airways was not affected by allergic inflammation or changes in humidity. At high relative humidity, the OVA-sensitized mice had a decreased expiratory airflow rate compared to the saline control mice after exposure to approximately 5 ppm FA. This is in accordance with the observations that asthmatics are more sensitive than non-asthmatics to higher concentrations of airway irritants including FA. In the dry environment, the opposite trend was seen; here, the saline control mice had a significantly decreased expiratory airflow rate compared to OVA-sensitized mice when exposed to 1.8 and 4 ppm FA. We speculate that increased mucus production in the OVA-sensitized mice has increased the “scrubber effect” in the nose, consequently protecting the conducting and lower airways. - Highlights: ► Role of air humidity and allergy on sensitivity to an airway irritant was studied. ► In the humid environment, allergy amplified the effects of formaldehyde. ► In the dry environment, allergy reduced the effect of formaldehyde. ► Neither allergy nor humidity changed the formaldehyde-induced nasal irritation.

Acute airway effects of airborne formaldehyde in sensitized and non-sensitized mice housed in a dry or humid environment

International Nuclear Information System (INIS)

Larsen, Søren Thor; Wolkoff, Peder; Hammer, Maria; Kofoed-Sørensen, Vivi; Clausen, Per Axel; Nielsen, Gunnar Damgård

2013-01-01

We investigated the role of air humidity and allergic sensitization on the acute airway response to inhaled formaldehyde (FA) vapor. Mice were sensitized to the immunogen ovalbumin (OVA) by three intraperitoneal injections followed by two aerosol challenges, giving rise to allergic airway inflammation. Control mice were sham sensitized by saline injections and challenged by saline aerosols. Once sensitized, the mice were housed at high (85–89%) or low (< 10%) relative humidity, respectively for 48 h prior to a 60-min exposure to either 0.4, 1.8 or about 5 ppm FA. Before, during and after exposure, breathing parameters were monitored. These included the specific markers of nose and lung irritations as well as the expiratory flow rate, the latter being a marker of airflow limitation. The sensory irritation response in the upper airways was not affected by allergic inflammation or changes in humidity. At high relative humidity, the OVA-sensitized mice had a decreased expiratory airflow rate compared to the saline control mice after exposure to approximately 5 ppm FA. This is in accordance with the observations that asthmatics are more sensitive than non-asthmatics to higher concentrations of airway irritants including FA. In the dry environment, the opposite trend was seen; here, the saline control mice had a significantly decreased expiratory airflow rate compared to OVA-sensitized mice when exposed to 1.8 and 4 ppm FA. We speculate that increased mucus production in the OVA-sensitized mice has increased the “scrubber effect” in the nose, consequently protecting the conducting and lower airways. - Highlights: ► Role of air humidity and allergy on sensitivity to an airway irritant was studied. ► In the humid environment, allergy amplified the effects of formaldehyde. ► In the dry environment, allergy reduced the effect of formaldehyde. ► Neither allergy nor humidity changed the formaldehyde-induced nasal irritation

Acute pulmonary schistosomiasis: Correlation between the high-resolution CT and pathological findings

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Arthur Soares Souza, Jr.

2007-09-01

Full Text Available A 35 years old rural worker presented with a 15 days history of progressive dyspnea, associated with dry cough, mialgia and fever. Few days before the symptoms, he had swim in a river. The chest radiographs demonstrated bilateral reticule-nodular infiltrates. The high-resolution CT showed patchy areas of ground-glass attenuation, irregular interlobular septal thickening, intralobular interstitial thickening, and small nodules, which are confluent in some regions. All the laboratorial investigation were negative. The open lung biopsy shows parenchymal granulomatous inflammation, and numerous schistosome ova. Resumo: Paciente masculino, de 35 anos, trabalhador rural, apresentando-se com história de dispneia progressiva, tosse seca, mialgia e febre, com evolução de 15 dias. Relatava ter nadado num rio, recentemente. As radiografias de tórax mostravam infiltração retículo-nodular bilateral. A tomografia computadorizada de alta resolução evidenciava áreas esparsas de atenuação em vidro fosco, espessamento irregular de septos in- terlobulares e do interstício intralobular e pequenos nódulos, confluentes em algumas regiões. Os exames laboratoriais eram normais. Biópsia pulmonar a céu aberto demonstrou inflamação parenquimatosa granulomatosa, com presença de ovos de esquistossoma. Key-words: Acute schistosomiasis, high-resolution computed tomography, parasitic infection, lungs, Palavras-chave: Esquistossomose aguda, tomografia computadorizada de alta resolução, infecção parasitária, pulmões

Antigen-Specific IgG ameliorates allergic airway inflammation via Fcγ receptor IIB on dendritic cells

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Karasuyama Hajime

2011-04-01

Full Text Available Abstract Background There have been few reports on the role of Fc receptors (FcRs and immunoglobulin G (IgG in asthma. The purpose of this study is to clarify the role of inhibitory FcRs and antigen presenting cells (APCs in pathogenesis of asthma and to evaluate antigen-transporting and presenting capacity by APCs in the tracheobronchial mucosa. Methods In FcγRIIB deficient (KO and C57BL/6 (WT mice, the effects of intratracheal instillation of antigen-specific IgG were analysed using the model with sensitization and airborne challenge with ovalbumin (OVA. Thoracic lymph nodes instilled with fluorescein-conjugated OVA were analysed by fluorescence microscopy. Moreover, we analysed the CD11c+ MHC class II+ cells which intaken fluorescein-conjugated OVA in thoracic lymph nodes by flow cytometry. Also, lung-derived CD11c+ APCs were analysed by flow cytometry. Effects of anti-OVA IgG1 on bone marrow dendritic cells (BMDCs in vitro were also analysed. Moreover, in FcγRIIB KO mice intravenously transplanted dendritic cells (DCs differentiated from BMDCs of WT mice, the effects of intratracheal instillation of anti-OVA IgG were evaluated by bronchoalveolar lavage (BAL. Results In WT mice, total cells and eosinophils in BAL fluid reduced after instillation with anti-OVA IgG1. Anti-OVA IgG1 suppressed airway inflammation in hyperresponsiveness and histology. In addition, the number of the fluorescein-conjugated OVA in CD11c+ MHC class II+ cells of thoracic lymph nodes with anti-OVA IgG1 instillation decreased compared with PBS. Also, MHC class II expression on lung-derived CD11c+ APCs with anti-OVA IgG1 instillation reduced. Moreover, in vitro, we showed that BMDCs with anti-OVA IgG1 significantly decreased the T cell proliferation. Finally, we demonstrated that the lacking effects of anti-OVA IgG1 on airway inflammation on FcγRIIB KO mice were restored with WT-derived BMDCs transplanted intravenously. Conclusion Antigen-specific IgG ameliorates

Routine focal mollusciciding after chemotherapy to control Schistosoma mansoni in Cul de Sac valley, Saint Lucia.

Science.gov (United States)

Barnish, G; Jordan, P; Bartholomew, R K; Grist, E

1982-01-01

Concluding results of a 10-year schistosomiasis control programme in Cul de Sac valley, Saint Lucia, are described. After an area-wide mollusciciding campaign (1970-75), and a surveillance/treatment programme supplemented with selective population chemotherapy in 1975 and 1976, prevalence rates of Schistosoma mansoni were reduced to low levels. To prevent a resurgence of transmission a cost effective routine focal mollusciciding programme, suitable for public health implementation was evaluated from 1977 to 1981. Streams and main collector drains in banana fields, considered to be potential S. mansoni transmission sites, were treated every four weeks with Bayluscide 6076 emulsifiable concentrate (Clonitralide). Snail populations were effectively controlled in the treated areas but large numbers were present where no treatment was given. Only 0 X 06% of sentinel snails became infected. Prevalence of infection in the human population remained low (over-all 5%) and intensity of infection at a level not normally associated with schistosomal disease. Since control started 10 years earlier the level of potential contamination has fallen by 92% in high transmission areas. The four-year programme cost US+12,909 of which 54% was for molluscicide, 27% for labour and 19% for transport, equipment and sundries. The average annual cost per head of population was US+0 X 46.

Age-related patterns in human myeloid dendritic cell populations in people exposed to Schistosoma haematobium infection.

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Norman Nausch

Full Text Available Urogenital schistosomiasis is caused by the helminth parasite Schistosoma haematobium. In high transmission areas, children acquire schistosome infection early in life with infection levels peaking in early childhood and subsequently declining in late childhood. This age-related infection profile is thought to result from the gradual development of protective acquired immunity. Age-related differences in schistosome-specific humoral and cellular responses have been reported from several field studies. However there has not yet been a systematic study of the age-related changes in human dendritic cells, the drivers of T cell polarisation.Peripheral blood mononuclear cells were obtained from a cohort of 61 Zimbabwean aged 5-45 years with a S. haematobium prevalence of 47.5%. Two subsets of dendritic cells, myeloid and plasmacytoid dendritic cells (mDCs and pDCs, were analyzed by flow cytometry.In this population, schistosome infection levels peaked in the youngest age group (5-9 years, and declined in late childhood and adulthood (10+ years. The proportions of both mDCs and pDCs varied with age. However, for mDCs the age profile depended on host infection status. In the youngest age group infected people had enhanced proportions of mDCs as well as lower levels of HLA-DR on mDCs than un-infected people. In the older age groups (10-13 and 14-45 years infected people had lower proportions of mDCs compared to un-infected individuals, but no infection status-related differences were observed in their levels of HLA-DR. Moreover mDC proportions correlated with levels of schistosome-specific IgG, which can be associated with protective immunity. In contrast proportions of pDCs varied with host age, but not with infection status.Our results show that dendritic cell proportions and activation in a human population living in schistosome-endemic areas vary with host age reflecting differences in cumulative history of exposure to schistosome infection.

Pharmaceutical formulations as immunological adjuvants

Energy Technology Data Exchange (ETDEWEB)

O' Hagan, D T

1987-01-01

The aim of this work was to enhance the immune responses to ovalbumin (OVA) following its oral administration, by the association of the protein with colloidal carriers, which may protect the protein from degradation in the gastrointestinal tract and/or facilitate its uptake across the intestine. An enzyme linked immunosorbent assay (ELISA) was established for the determination of rat anti-OVA antibodies and an immunization protocol was established to induce a statistically significant salivary antibody response to OVA in the rat. A radioimmunoassay for the determination of rat anti-OVA antibodies was also established, to confirm the ELISA results. Methods were established to determine the extent of incorporation or adsorption of OVA into or onto the colloidal carrier formations.

A polysaccharide isolated from Agaricus blazei Murill (ABP-AW1) as a potential Th1 immunity-stimulating adjuvant.

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Cui, Liran; Sun, Yongxu; Xu, Hao; Xu, Huiyu; Cong, Huan; Liu, Jicheng

2013-10-01

In the present study, a low molecular weight polysaccharide, ABP-AW1, isolated from Agaricus blazei Murill was assessed for its potential adjuvant activity. ABP-AW1 is considered to create a 'depot' of antigen at a subcutaneous injection site. ICR mice were immunized with 100 μg ovalbumin (OVA) alone or with 100 μg OVA formulated in 0.9% saline containing 200 μg aluminum (alum) or ABP-AW1 (50, 100 and 200 μg) on days 1 and 15. Two weeks after the secondary immunization, splenocyte proliferation, the expression of surface markers, cytokine production and the OVA-specific antibody levels in the serum were determined. The OVA/ABP-AW1 vaccine, in comparison with OVA alone, markedly increased the proliferation of splenic lymphocytes and elicited greater antigen-specific CD4 + T cell activation, as determined by splenic CD4 + CD69 + T cells and Th1 cytokine interferon (IFN)-γ release. The combination of ABP-AW1 and OVA also enhanced IgG2b antibody responses to OVA. In conclusion, these data indicated that ABP-AW1 significantly enhanced the humoral and cellular immune responses against OVA in the mice, suggesting that ABP-AW1 stimulated Th1-type immunity. We suggest that ABP-AW1 may serve as a new adjuvant.

Whole-organ isolation approach as a basis for tissue-specific analyses in Schistosoma mansoni.

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Steffen Hahnel

Full Text Available BACKGROUND: Schistosomiasis is one of the most important parasitic diseases worldwide, second only to malaria. Schistosomes exhibit an exceptional reproductive biology since the sexual maturation of the female, which includes the differentiation of the reproductive organs, is controlled by pairing. Pathogenicity originates from eggs, which cause severe inflammation in their hosts. Elucidation of processes contributing to female maturation is not only of interest to basic science but also considering novel concepts combating schistosomiasis. METHODOLOGY/PRINCIPAL FINDINGS: To get direct access to the reproductive organs, we established a novel protocol using a combined detergent/protease-treatment removing the tegument and the musculature of adult Schistosoma mansoni. All steps were monitored by scanning electron microscopy (SEM and bright-field microscopy (BF. We focused on the gonads of adult schistosomes and demonstrated that isolated and purified testes and ovaries can be used for morphological and structural studies as well as sources for RNA and protein of sufficient amounts for subsequent analyses such as RT-PCR and immunoblotting. To this end, first exemplary evidence was obtained for tissue-specific transcription within the gonads (axonemal dynein intermediate chain gene SmAxDynIC; aquaporin gene SmAQP as well as for post-transcriptional regulation (SmAQP. CONCLUSIONS/SIGNIFICANCE: The presented method provides a new way of getting access to tissue-specific material of S. mansoni. With regard to many still unanswered questions of schistosome biology, such as elucidating the molecular processes involved in schistosome reproduction, this protocol provides opportunities for, e.g., sub-transcriptomics and sub-proteomics at the organ level. This will promote the characterisation of gene-expression profiles, or more specifically to complete knowledge of signalling pathways contributing to differentiation processes, so discovering involved

Imatinib treatment causes substantial transcriptional changes in adult Schistosoma mansoni in vitro exhibiting pleiotropic effects.

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Christin Buro

2014-06-01

Full Text Available Schistosome parasites cause schistosomiasis, one of the most important infectious diseases worldwide. For decades Praziquantel (PZQ is the only drug widely used for controlling schistosomiasis. The absence of a vaccine and fear of PZQ resistance have motivated the search for alternatives. Studies on protein kinases (PKs demonstrated their importance for diverse physiological processes in schistosomes. Among others two Abl tyrosine kinases, SmAbl1 and SmAbl2, were identified in Schistosoma mansoni and shown to be transcribed in the gonads and the gastrodermis. SmAbl1 activity was blocked by Imatinib, a known Abl-TK inhibitor used in human cancer therapy (Gleevec/Glivec. Imatinib exhibited dramatic effects on the morphology and physiology of adult schistosomes in vitro causing the death of the parasites.Here we show modeling data supporting the targeting of SmAbl1/2 by Imatinib. A biochemical assay confirmed that SmAbl2 activity is also inhibited by Imatinib. Microarray analyses and qRT-PCR experiments were done to unravel transcriptional processes influenced by Imatinib in adult schistosomes in vitro demonstrating a wide influence on worm physiology. Surface-, muscle-, gut and gonad-associated processes were affected as evidenced by the differential transcription of e.g. the gynecophoral canal protein gene GCP, paramyosin, titin, hemoglobinase, and cathepsins. Furthermore, transcript levels of VAL-7 and egg formation-associated genes such as tyrosinase 1, p14, and fs800-like were affected as well as those of signaling genes including a ribosomal protein S6 kinase and a glutamate receptor. Finally, a comparative in silico analysis of the obtained microarray data sets and previous data analyzing the effect of a TGFβR1 inhibitor on transcription provided first evidence for an association of TGFβ and Abl kinase signaling. Among others GCP and egg formation-associated genes were identified as common targets.The data affirm broad negative effects of

Antigen-specific and non-specific CD4+ T cell recruitment and proliferation during influenza infection

International Nuclear Information System (INIS)

Chapman, Timothy J.; Castrucci, Maria R.; Padrick, Ryan C.; Bradley, Linda M.; Topham, David J.

2005-01-01

To track epitope-specific CD4 + T cells at a single-cell level during influenza infection, the MHC class II-restricted OVA 323-339 epitope was engineered into the neuraminidase stalk of influenza/A/WSN, creating a surrogate viral antigen. The recombinant virus, influenza A/WSN/OVA II , replicated well, was cleared normally, and stimulated both wild-type and DO11.10 or OT-II TCR transgenic OVA-specific CD4 + T cells. OVA-specific CD4 T cells proliferated during infection only when the OVA epitope was present. However, previously primed (but not naive) transgenic CD4 + T cells were recruited to the infected lung both in the presence and absence of the OVA 323-339 epitope. These data show that, when primed, CD4 + T cells may traffic to the lung in the absence of antigen, but do not proliferate. These results also document a useful tool for the study of CD4 T cells in influenza infection

Pulmonary toxicity and adjuvant effect of di-(2-exylhexyl phthalate in ovalbumin-immunized BALB/c mice.

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Jing Guo

Full Text Available BACKGROUND: Asthma is a complex pulmonary inflammatory disease, which is characterized by airway hyperresponsiveness, variable airflow obstruction and inflammation in the airways. The majority of asthma is allergic asthma, which is a disease caused by type I hypersensitivity mediated by IgE. Exposures to a number of environmental chemicals are suspected to lead to asthma, one such pollutant is di-(2-ethylheyl phthalate (DEHP. DEHP is a manufactured chemical that is commonly added in plastic products to make them flexible. Epidemiological studies have revealed a positive association between DEHP exposure and asthma prevalence. METHODOLOGY/PRINCIPAL FINDINGS: The present study was aimed to determine the underlying role of DEHP exposure in airway reactivity, especially when combined with allergen exposure. The biomarkers include pulmonary histopathology, airway hyperresponsiveness (lung function, IgE, IL-4, IFN-γ and eosinophils. Healthy balb/c mice were randomly divided into eight exposure groups (n = 8 each: (1 saline control, (2 30 µg/(kg•d DEHP, (3 300 µg/(kg•d DEHP, (4 3000 µg/(kg•d DEHP, and (5 ovalbumin (OVA-sensitized group, (6 OVA-combined with 30 µg/(kg•d DEHP, (7 OVA-combined with 300 µg/(kg•d DEHP, and (8 OVA-combined with 3000 µg/(kg•d DEHP. Experimental tests were conducted after 52-day DEHP exposure and subsequently one week of challenge with aerosolized OVA. The principal findings include: (1 Strong postive associations exist between OVA-combined DEHP exposure and serum total IgE (T-IgE, as well as histological findings. These positive associations show a dose-dependent low dose sensitive effect of DEHP. (2 IL-4, eosinophil recruitment and lung function are also indicators for adjuvant effect of DEHP. CONCLUSIONS/SIGNIFICANCE: Our results suggest that except the significant changes of immunological and inflammatory biomarkers (T-IgE, IL-4, IFN-γ and eosinophils, the pulmonary histological (histopathological

Bacterial derived proteoliposome as ideal delivery system and cellular adjuvant.

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Rodríguez, Tamara; Pérez, Oliver a; Ugrinovic, Sanja; Bracho, Gustavo; Mastroeni, Pietro

2006-04-12

We explored the potential of a proteoliposome (PL) from the outer membrane of N. meningitidis B, as an immunopotentiator and as a vector for antigen delivery to dendritic cells (DC). DC were incubated with PL resulting in up-regulation of MHC-II, CD40, CD80, and CD86 expression and production of TNFalpha and IL12(p70). Ovoalbumin (OVA) was incorporated within PL (PL-OVA). PL-OVA presented OVA-specific peptides to CD4+ and CD8+ OVA-specific T-cell hybridomas. PL exerts an immunomodulatory effect on DC and is a general system to deliver antigens for presentation to CD4+ and CD8+ T-cells possibly implicated in the induction CD8+ cytotoxic T lymphocytes (CTLs) responses.

Toll-like receptor-2 agonist-allergen coupling efficiently redirects Th2 cell responses and inhibits allergic airway eosinophilia.

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Krishnaswamy, Jayendra Kumar; Jirmo, Adan Chari; Baru, Abdul Mannan; Ebensen, Thomas; Guzmán, Carlos A; Sparwasser, Tim; Behrens, Georg M N

2012-12-01

Toll-like receptor (TLR) agonists beneficially modulate allergic airway inflammation. However, the efficiency of TLR agonists varies considerably, and their exact cellular mechanisms (especially of TLR 2/6 agonists) are incompletely understood. We investigated at a cellular level whether the administration of the pharmacologically improved TLR2/6 agonist S-[2,3-bispalmitoyiloxy-(2R)-propyl]-R-cysteinyl-amido-monomethoxy polyethylene glycol (BPP) conjugated to antigenic peptide (BPP-OVA) could divert an existing Th2 response and influence airway eosinophilia. The effects of BPP-OVA on airway inflammation were assessed in a classic murine sensitization/challenge model and an adoptive transfer model, which involved the adoptive transfer of in vitro differentiated ovalbumin (OVA)-specific Th2 cells. Functional T-cell stimulation by lung dendritic cells (DCs) was determined both in vitro and in vivo, combined with a cytokine secretion analysis. A single mucosal application of BPP-OVA efficiently delivered antigen, led to TLR2-mediated DC activation, and resulted in OVA-specific T-cell proliferation via lung DCs in vivo. In alternative models of allergic airway disease, a single administration of BPP-OVA before OVA challenge (but not BPP alone) significantly reduced airway eosinophilia, most likely through altered antigen-specific T-cell stimulation via DCs. Analyses of adoptively transferred Th2-biased cells after BPP-OVA administration in vivo suggested that BPP-OVA guides antigen-specific Th2 cells to produce significantly higher amounts of IFN-γ upon allergen challenge. In conclusion, our data show for the first time that a single mucosal administration of a TLR 2/6 agonist-allergen conjugate can provoke IFN-γ responses in Th2-biased cells and alleviate allergic airway inflammation.

Polymer nanoparticles for cross-presentation of exogenous antigens and enhanced cytotoxic T-lymphocyte immune response

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Song C

2016-08-01

Full Text Available Chanyoung Song,* Young-Woock Noh,* Yong Taik Lim SKKU Advanced Institute of Nanotechnology (SAINT, School of Chemical Engineering, Sungkyunkwan University, Suwon, South Korea *These authors contributed equally to this work Abstract: Effective induction of an antigen-specific cytotoxic T lymphocyte (CTL immune response is one of the key goals of cancer immunotherapy. We report the design and fabrication of polyethylenimine (PEI-coated polymer nanoparticles (NPs as efficient antigen-delivery carriers that can induce antigen cross-presentation and a strong CTL response. After synthesis of poly(d,l-lactide-co-glycolide (PLGA NPs containing ovalbumin (OVA by the double-emulsion solvent-evaporation method, cationic-charged PLGA NPs were generated by coating them with PEI. In a methyl tetrazolium salt assay, no discernible cytotoxic effect of PEI-coated PLGA (OVA NPs was observed. The capacity and mechanism of PEI-coated PLGA (OVA NPs for antigen delivery and cross-presentation on dendritic cells (DCs were determined by fluorescence microscopy and flow cytometry. PEI-coated PLGA (OVA NPs were internalized efficiently via phagocytosis or macropinocytosis in DCs and induced efficient cross-presentation of the antigen on MHC class I molecules via both endosome escape and a lysosomal processing mechanism. The DCs treated with PEI-coated PLGA (OVA NPs induced a release of IL-2 cytokine from OVA-specific CD8-OVA1.3 T cells more efficiently than DCs treated with PLGA (OVA NPs. Therefore, the PEI-coated PLGA (OVA NPs can induce antigen cross-presentation and are expected to be used for induction of a strong CTL immune response and for efficient anticancer immunotherapy. Keywords: antigen delivery, dendritic cells, polymer NPs, vaccine, cross-presentation

Development and validation of a quantitative, high-throughput, fluorescent-based bioassay to detect schistosoma viability.

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Emily Peak

2010-07-01

Full Text Available Schistosomiasis, caused by infection with the blood fluke Schistosoma, is responsible for greater than 200,000 human deaths per annum. Objective high-throughput screens for detecting novel anti-schistosomal targets will drive 'genome to drug' lead translational science at an unprecedented rate. Current methods for detecting schistosome viability rely on qualitative microscopic criteria, which require an understanding of parasite morphology, and most importantly, must be subjectively interpreted. These limitations, in the current state of the art, have significantly impeded progress into whole schistosome screening for next generation chemotherapies.We present here a microtiter plate-based method for reproducibly detecting schistosomula viability that takes advantage of the differential uptake of fluorophores (propidium iodide and fluorescein diacetate by living organisms. We validate this high-throughput system in detecting schistosomula viability using auranofin (a known inhibitor of thioredoxin glutathione reductase, praziquantel and a range of small compounds with previously-described (gambogic acid, sodium salinomycin, ethinyl estradiol, fluoxetidine hydrochloride, miconazole nitrate, chlorpromazine hydrochloride, amphotericin b, niclosamide or suggested (bepridil, ciclopirox, rescinnamine, flucytosine, vinblastine and carbidopa anti-schistosomal activities. This developed method is sensitive (200 schistosomula/well can be assayed, relevant to industrial (384-well microtiter plate compatibility and academic (96-well microtiter plate compatibility settings, translatable to functional genomics screens and drug assays, does not require a priori knowledge of schistosome biology and is quantitative.The wide-scale application of this fluorescence-based bioassay will greatly accelerate the objective identification of novel therapeutic lead targets/compounds to combat schistosomiasis. Adapting this bioassay for use with other parasitic worm species

Bromelain Inhibits Allergic Sensitization and Murine Asthma via Modulation of Dendritic Cells

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Eric R. Secor

2013-01-01

Full Text Available The incidence of atopic conditions has increased in industrialized countries. Persisting symptoms and concern for drug side-effects lead patients toward adjunctive treatments such as phytotherapy. Previously, we have shown that Bromelain (sBr, a mixture of cysteine proteases from pineapple, Ananas comosus, inhibits ovalbumin (OVA-induced murine model of allergic airway disease (AAD. However, sBr’s effect on development of AAD when treatment is administered throughout OVA-alum sensitization was unknown and is the aim of the present study. C57BL/6J mice were sensitized with OVA/alum and challenged with 7 days OVA aerosol. sBr 6 mg/kg/0.5 ml or PBS vehicle were administered throughout sensitization. Lung, bronchoalveolar lavage (BAL, spleen, and lymph nodes were processed for flow cytometry and OVA-specific IgE was determined via ELISA. sBr treatment throughout OVA-alum sensitization significantly reduced the development of AAD (BAL eosinophils and lymphocytes. OVA-specific IgE and OVA TET+ cells were decreased. sBr reduced CD11c+ dendritic cell subsets, and in vitro treatment of DCs significantly reduced CD44, a key receptor in both cell trafficking and activation. sBr was shown to reduce allergic sensitization and the generation of AAD upon antigen challenge. These results provide additional insight into sBr's anti-inflammatory and antiallergic properties and rationale for translation into the clinical arena.

Pathogenicity of Trichobilharzia spp. for Vertebrates

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Lichtenbergová Lucie

2012-01-01

Full Text Available Bird schistosomes, besides being responsible for bird schistosomiasis, are known as causative agents of cercarial dermatitis. Cercarial dermatitis develops after repeated contact with cercariae, mainly of the genus Trichobilharzia, and was described as a type I, immediate hypersensitivity response, followed by a late phase reaction. The immune response is Th2 polarized. Primary infection leads to an inflammatory reaction that is insufficient to eliminate the schistosomes and schistosomula may continue its migration through the body of avian as well as mammalian hosts. However, reinfections of experimental mice revealed an immune reaction leading to destruction of the majority of schistosomula in the skin. Infection with the nasal schistosome Trichobilharzia regenti probably represents a higher health risk than infections with visceral schistosomes. After the skin penetration by the cercariae, parasites migrate via the peripheral nerves, spinal cord to the brain, and terminate their life cycle in the nasal mucosa of waterfowl where they lay eggs. T. regenti can also get over skin barrier and migrate to CNS of experimental mice. During heavy infections, neuroinfections of both birds and mammals lead to the development of a cellular immune response and axonal damage in the vicinity of the schistosomulum. Such infections are manifest by neuromotor disorders.

An inducible transgenic mouse model for immune mediated hepatitis showing clearance of antigen expressing hepatocytes by CD8+ T cells.

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Marcin Cebula

Full Text Available The liver has the ability to prime immune responses against neo antigens provided upon infections. However, T cell immunity in liver is uniquely modulated by the complex tolerogenic property of this organ that has to also cope with foreign agents such as endotoxins or food antigens. In this respect, the nature of intrahepatic T cell responses remains to be fully characterized. To gain deeper insight into the mechanisms that regulate the CD8+ T cell responses in the liver, we established a novel OVA_X_CreER(T2 mouse model. Upon tamoxifen administration OVA antigen expression is observed in a fraction of hepatocytes, resulting in a mosaic expression pattern. To elucidate the cross-talk of CD8+ T cells with antigen-expressing hepatocytes, we adoptively transferred K(b/OVA257-264-specific OT-I T cells to OVA_X_CreER(T2 mice or generated triple transgenic OVA_X CreER(T2_X_OT-I mice. OT-I T cells become activated in OVA_X_CreER(T2 mice and induce an acute and transient hepatitis accompanied by liver damage. In OVA_X_CreER(T2_X_OT-I mice, OVA induction triggers an OT-I T cell mediated, fulminant hepatitis resulting in 50% mortality. Surviving mice manifest a long lasting hepatitis, and recover after 9 weeks. In these experimental settings, recovery from hepatitis correlates with a complete loss of OVA expression indicating efficient clearance of the antigen-expressing hepatocytes. Moreover, a relapse of hepatitis can be induced upon re-induction of cured OVA_X_CreER(T2_X_OT-I mice indicating absence of tolerogenic mechanisms. This pathogen-free, conditional mouse model has the advantage of tamoxifen inducible tissue specific antigen expression that reflects the heterogeneity of viral antigen expression and enables the study of intrahepatic immune responses to both de novo and persistent antigen. It allows following the course of intrahepatic immune responses: initiation, the acute phase and antigen clearance.

Comparison of chitosan nanoparticles and chitosan hydrogels for vaccine delivery

DEFF Research Database (Denmark)

Gordon, Sarah; Saupe, Anne; McBurney, Warren

2008-01-01

In this work the potential of chitosan nanoparticles (CNP) and thermosensitive chitosan hydrogels as particulate and sustained release vaccine delivery systems was investigated. CNP and chitosan hydrogels were prepared, loaded with the model protein antigen ovalbumin (OVA) and characterised...... of the release of fluorescently-labelled OVA (FITC-OVA) from CNP and chitosan hydrogels in-vitro showed that approximately 50% of the total protein was released from CNP within a period of ten days; release of antigen from chitosan gel occurred in a more sustained manner, with ... released after 10 days. The slow release from gel formulations may be explained by the strong interactions of the protein with chitosan. While OVA-loaded CNP showed no significant immunogenicity, formulations of OVA in chitosan gel were able to stimulate both cell-mediated and humoral immunity in-vivo....

Asian sand dust enhances ovalbumin-induced eosinophil recruitment in the alveoli and airway of mice

International Nuclear Information System (INIS)

Hiyoshi, Kyoko; Ichinose, Takamichi; Sadakane, Kaori; Takano, Hirohisa; Nishikawa, Masataka; Mori, Ikuko; Yanagisawa, Rie; Yoshida, Seiichi; Kumagai, Yoshito; Tomura, Shigeo; Shibamoto, Takayuki

2005-01-01

Asian sand dust (ASD) containing sulfate (SO 4 2- ) reportedly causes adverse respiratory health effects but there is no experimental study showing the effect of ASD toward allergic respiratory diseases. The effects of ASD and ASD plus SO 4 2- toward allergic lung inflammation induced by ovalbumin (OVA) were investigated in this study. ICR mice were administered intratracheally with saline; ASD alone (sample from Shapotou desert); and ASD plus SO 4 2- (ASD-SO 4 ); OVA+ASD; OVA+ASD-SO 4 . ASD or ASD-SO 4 alone caused mild nutrophilic inflammation in the bronchi and alveoli. ASD and ASD-SO 4 increased pro-inflammatory mediators, such as Keratinocyte chemoattractant (KC) and macrophage inflammatory protein (MIP)-1 alpha, in bronchoalveolar lavage fluids (BALF). ASD and ASD-SO 4 enhanced eosinophil recruitment induced by OVA in the alveoli and in the submucosa of the airway, which has a goblet cell proliferation in the bronchial epithelium. However, a further increase of eosinophils by addition of SO 4 2- was not observed. The two sand dusts synergistically increased interleukin-5 (IL-5) and monocyte chemotactic protein-1 (MCP-1), which were associated with OVA, in BALF. However, the increased levels of IL-5 were lower in the OVA+ASD-SO 4 group than in the OVA+ASD group. ASD caused the adjuvant effects to specific-IgG1 production by OVA, but not to specific-IgE. These results suggest that the enhancement of eosinophil recruitment in the lung is mediated by synergistically increased IL-5 and MCP-1. IgG1 antibodies may play an important role in the enhancement of allergic reaction caused by OVA and sand dust. However, extra sulfate may not contribute to an increase of eosinophils

An oral sensitization model in Brown Norway rats to screen for potential allergenicity of food proteins

NARCIS (Netherlands)

Knippels, L.M.J.; Houben, G.F.; Spanhaak, S.; Penninks, A.H.

1999-01-01

We developed an oral sensitization protocol for food proteins for the rat. Young Brown Norway (BN) rats were exposed to 1 mg ovalbumin (OVA) by daily gavage dosing for 42 days without the use of an adjuvant. OVA-specific IgE and IgG responses were determined by ELISA. On an oral challenge with OVA

Evaluation of field recognizable morbidity indicators of Schistosoma haematobium infection among primary school children in Ghana

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Ato Kwamena Tetteh

2016-09-01

Materials and Methods — In all, 417 pupils in three primary schools (Kasseh sub-District, Dangme East District, Ghana, provided urine samples, which were examined for S. haematobium ova. The study utilized a structured questionnaire, the Urit 10V multi-stick urine reagent strips and the filtration method. Results — Overall, prevalence by microscopy was 20.9% (requires targeted treatment once every two years, and was higher (14.0% among the 10-15 years age group (χ2=22.44, p<0.001. The lowest prevalence was among the <6 (0.5%, 2/417 and ≥19 (1.4%, 6/417 years age groups. There was no significant difference in prevalence among females (7.9%, 33/417 and males (12.9%, 54/417 (χ2=2.58, p=0.108. Self-reported haematuria was 43.2% (targeted treatment once a year. There was a significant difference between female (16.1%, 67/417 and male (27.1%, 113/417 responses to self-reported haematuria (χ2=4.170, p<0.001. A lower consolidated mean prevalence of 11.7% was estimated among pupils who had ova in their urine and also exhibited three morbidity indicators (haematuria, leucocyturia and proteinuria. Combined and averaged sensitivity and specificity estimations (sensitivity = 55.4%, specificity = 67.8%, Positive Predictive Value (PPV = 53.4%, Negative Predictive Value (NPV = 64.2% of these morbidity indicators, was insufficient in equalizing the reliability of ova quantification. With the exception of leucocyturia, which was common among all pupils, 28.75% (25/87 of the infected individuals did not have any form of haematuria or proteinuria. Out of these, one pupil had heavy ova intensity (80 eggs/10ml of urine while the remaining 24 had low ova intensity infection (1-44 eggs/10ml of urine. Questionnaire correctly identified 56.3% of pupils with S. haematobium ova in their urine, also reporting bloody urine (PPV=27.2%; NPV=84.0%. It also identified 49.4% of pupils with ova, reporting painful urination (PPV=26.1%, NPV=82.5%. Conclusion — This study emphasizes the

Glycomic Analysis of Life Stages of the Human Parasite Schistosoma mansoni Reveals Developmental Expression Profiles of Functional and Antigenic Glycan Motifs.

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Smit, Cornelis H; van Diepen, Angela; Nguyen, D Linh; Wuhrer, Manfred; Hoffmann, Karl F; Deelder, André M; Hokke, Cornelis H

2015-07-01

Glycans present on glycoproteins and glycolipids of the major human parasite Schistosoma mansoni induce innate as well as adaptive immune responses in the host. To be able to study the molecular characteristics of schistosome infections it is therefore required to determine the expression profiles of glycans and antigenic glycan-motifs during a range of critical stages of the complex schistosome lifecycle. We performed a longitudinal profiling study covering schistosome glycosylation throughout worm- and egg-development using a mass spectrometry-based glycomics approach. Our study revealed that during worm development N-glycans with Galβ1-4(Fucα1-3)GlcNAc (LeX) and core-xylose motifs were rapidly lost after cercariae to schistosomula transformation, whereas GalNAcβ1-4GlcNAc (LDN)-motifs gradually became abundant and predominated in adult worms. LeX-motifs were present on glycolipids up to 2 weeks of schistosomula development, whereas glycolipids with mono- and multifucosylated LDN-motifs remained present up to the adult worm stage. In contrast, expression of complex O-glycans diminished to undetectable levels within days after transformation. During egg development, a rich diversity of N-glycans with fucosylated motifs was expressed, but with α3-core fucose and a high degree of multifucosylated antennae only in mature eggs and miracidia. N-glycan antennae were exclusively LDN-based in miracidia. O-glycans in the mature eggs were also diverse and contained LeX- and multifucosylated LDN, but none of these were associated with miracidia in which we detected only the Galβ1-3(Galβ1-6)GalNAc core glycan. Immature eggs also exhibited short O-glycan core structures only, suggesting that complex fucosylated O-glycans of schistosome eggs are derived primarily from glycoproteins produced by the subshell envelope in the developed egg. Lipid glycans with multifucosylated GlcNAc repeats were present throughout egg development, but with the longer highly fucosylated

Developmental gene expression profiles of the human pathogen Schistosoma japonicum

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McManus Donald P

2009-03-01

Full Text Available Abstract Background The schistosome blood flukes are complex trematodes and cause a chronic parasitic disease of significant public health importance worldwide, schistosomiasis. Their life cycle is characterised by distinct parasitic and free-living phases involving mammalian and snail hosts and freshwater. Microarray analysis was used to profile developmental gene expression in the Asian species, Schistosoma japonicum. Total RNAs were isolated from the three distinct environmental phases of the lifecycle – aquatic/snail (eggs, miracidia, sporocysts, cercariae, juvenile (lung schistosomula and paired but pre-egg laying adults and adult (paired, mature males and egg-producing females, both examined separately. Advanced analyses including ANOVA, principal component analysis, and hierarchal clustering provided a global synopsis of gene expression relationships among the different developmental stages of the schistosome parasite. Results Gene expression profiles were linked to the major environmental settings through which the developmental stages of the fluke have to adapt during the course of its life cycle. Gene ontologies of the differentially expressed genes revealed a wide range of functions and processes. In addition, stage-specific, differentially expressed genes were identified that were involved in numerous biological pathways and functions including calcium signalling, sphingolipid metabolism and parasite defence. Conclusion The findings provide a comprehensive database of gene expression in an important human pathogen, including transcriptional changes in genes involved in evasion of the host immune response, nutrient acquisition, energy production, calcium signalling, sphingolipid metabolism, egg production and tegumental function during development. This resource should help facilitate the identification and prioritization of new anti-schistosome drug and vaccine targets for the control of schistosomiasis.

15-lipoxygenase metabolites play an important role in the development of a T-helper type 1 allergic inflammation induced by double-stranded RNA.

Science.gov (United States)

Jeon, S G; Moon, H-G; Kim, Y-S; Choi, J-P; Shin, T-S; Hong, S-W; Tae, Y-M; Kim, S-H; Zhu, Z; Gho, Y S; Kim, Y-K

2009-06-01

We recently demonstrated that the T-helper type 1 (Th1) immune response plays an important role in the development of non-eosinophilic inflammation induced by airway exposure of an allergen plus double-stranded RNA (dsRNA). However, the role of lipoxygenase (LO) metabolites in the development of Th1 inflammation is poorly understood. To evaluate the role of LO metabolites in the development of Th1 inflammation induced by sensitization with an allergen plus dsRNA. A Th2-allergic inflammation mouse model was created by an intraperitoneal injection of lipopolysaccharide-depleted ovalbumin (OVA, 75 microg) and alum (2 mg) twice, and the Th1 model was created by intranasal application of OVA (75 microg) and synthetic dsRNA [10 microg of poly(I : C)] four times, followed by an intranasal challenge with 50 microg of OVA four times. The role of LO metabolites was evaluated using two approaches: a transgenic approach using 5-LO(-/-) and 15-LO(-/-) mice, and a pharmacological approach using inhibitors of cysteinyl leucotriene receptor-1 (cysLTR1), LTB4 receptor (BLT1), and 15-LO. We found that the Th1-allergic inflammation induced by OVA+dsRNA sensitization was similar between 5-LO(-/-) and wild-type (WT) control mice, although Th2 inflammation induced by sensitization with OVA+alum was reduced in the former group. In addition, dsRNA-induced Th1 allergic inflammation, which is associated with down-regulation of 15-hydroxyeicosateraenoic acids production, was not affected by treatment with cysLTR1 or BLT1 inhibitors, whereas it was significantly lower in 12/15-LO(-/-) mice compared with WT control mice. Moreover, dsRNA-induced allergic inflammation and the recruitment of T cells following an allergen challenge were significantly inhibited by treatment with a specific 15-LO inhibitor (PD146176). 15-LO metabolites appear to be important mediators in the development of Th1-allergic inflammation induced by sensitization with an allergen plus dsRNA. Our findings suggest that the

Comprehensive Transcriptome Analysis of Sex-Biased Expressed Genes Reveals Discrete Biological and Physiological Features of Male and Female Schistosoma japonicum.

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Pengfei Cai

2016-04-01

Full Text Available Schistosomiasis is a chronic and debilitating disease caused by blood flukes (digenetic trematodes of the genus Schistosoma. Schistosomes are sexually dimorphic and exhibit dramatic morphological changes during a complex lifecycle which requires subtle gene regulatory mechanisms to fulfil these complex biological processes. In the current study, a 41,982 features custom DNA microarray, which represents the most comprehensive probe coverage for any schistosome transcriptome study, was designed based on public domain and local databases to explore differential gene expression in S. japonicum. We found that approximately 1/10 of the total annotated genes in the S. japonicum genome are differentially expressed between adult males and females. In general, genes associated with the cytoskeleton, and motor and neuronal activities were readily expressed in male adult worms, whereas genes involved in amino acid metabolism, nucleotide biosynthesis, gluconeogenesis, glycosylation, cell cycle processes, DNA synthesis and genome fidelity and stability were enriched in females. Further, miRNAs target sites within these gene sets were predicted, which provides a scenario whereby the miRNAs potentially regulate these sex-biased expressed genes. The study significantly expands the expressional and regulatory characteristics of gender-biased expressed genes in schistosomes with high accuracy. The data provide a better appreciation of the biological and physiological features of male and female schistosome parasites, which may lead to novel vaccine targets and the development of new therapeutic interventions.

Comprehensive Transcriptome Analysis of Sex-Biased Expressed Genes Reveals Discrete Biological and Physiological Features of Male and Female Schistosoma japonicum.

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Cai, Pengfei; Liu, Shuai; Piao, Xianyu; Hou, Nan; Gobert, Geoffrey N; McManus, Donald P; Chen, Qijun

2016-04-01

Schistosomiasis is a chronic and debilitating disease caused by blood flukes (digenetic trematodes) of the genus Schistosoma. Schistosomes are sexually dimorphic and exhibit dramatic morphological changes during a complex lifecycle which requires subtle gene regulatory mechanisms to fulfil these complex biological processes. In the current study, a 41,982 features custom DNA microarray, which represents the most comprehensive probe coverage for any schistosome transcriptome study, was designed based on public domain and local databases to explore differential gene expression in S. japonicum. We found that approximately 1/10 of the total annotated genes in the S. japonicum genome are differentially expressed between adult males and females. In general, genes associated with the cytoskeleton, and motor and neuronal activities were readily expressed in male adult worms, whereas genes involved in amino acid metabolism, nucleotide biosynthesis, gluconeogenesis, glycosylation, cell cycle processes, DNA synthesis and genome fidelity and stability were enriched in females. Further, miRNAs target sites within these gene sets were predicted, which provides a scenario whereby the miRNAs potentially regulate these sex-biased expressed genes. The study significantly expands the expressional and regulatory characteristics of gender-biased expressed genes in schistosomes with high accuracy. The data provide a better appreciation of the biological and physiological features of male and female schistosome parasites, which may lead to novel vaccine targets and the development of new therapeutic interventions.

Natural Products as Leads in Schistosome Drug Discovery

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Bruno J. Neves

2015-01-01

Full Text Available Schistosomiasis is a neglected parasitic tropical disease that claims around 200,000 human lives every year. Praziquantel (PZQ, the only drug recommended by the World Health Organization for the treatment and control of human schistosomiasis, is now facing the threat of drug resistance, indicating the urgent need for new effective compounds to treat this disease. Therefore, globally, there is renewed interest in natural products (NPs as a starting point for drug discovery and development for schistosomiasis. Recent advances in genomics, proteomics, bioinformatics, and cheminformatics have brought about unprecedented opportunities for the rapid and more cost-effective discovery of new bioactive compounds against neglected tropical diseases. This review highlights the main contributions that NP drug discovery and development have made in the treatment of schistosomiasis and it discusses how integration with virtual screening (VS strategies may contribute to accelerating the development of new schistosomidal leads, especially through the identification of unexplored, biologically active chemical scaffolds and structural optimization of NPs with previously established activity.

Hesperetin-5,7,3'-O-triacetate suppresses airway hyperresponsiveness in ovalbumin-sensitized and challenged mice without reversing xylazine/ketamine-induced anesthesia in normal mice.

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Yang, You-Lan; Chen, Chi-Li; Chen, Chi-Ming; Ko, Wun-Chang

2017-05-30

We recently reported that hesperetin-5,7,3'-O-triacetate (HTA) dually inhibited phosphodiesterase (PDE)3/4 with a therapeutic ratio of 20.8. The application and development of PDE4 inhibitors for treating asthma or COPD are limited by their side effects, such as nausea, vomiting and gastric hypersecretion. PDE4 inhibitors were reported to reverse xylazine/ketamine-induced anesthesia in rats and triggered vomiting in ferrets. Thus the reversing effect of HTA on xylazine/ketamine-induced anesthesia in mice was studied to assess emetic effect of HTA. The aim of this study was to prove the therapeutic effect of HTA without vomiting effect at an effective dose for treating COPD. Ten female BALB/c mice in each group were sensitized by ovalbumin (OVA) on days 0 and 14. On day 21, these mice were emphasized the sensitization by Freund's complete adjuvant. Mice were challenged by 1% OVA nebulization on days 28, 29, and 30. Airway hyperresponsiveness (AHR) was assessed on day 32 in each group, using the FlexiVent system to determine airway resistance (R L ) and lung dynamic compliance (C dyn ) in anesthetized ovalbumin (OVA)-sensitized and challenged mice. Each group was orally administered HTA (10 ~ 100 μmol/kg), roflumilast (1 and 5 mg/kg) or vehicles (controls) 2 h before and 6 and 24 h after OVA provocation. For comparison, sham-treated mice were challenged with saline instead of 1% OVA. The ability to reverse xylazine/ketamine-induced anesthesia by HTA or roflumilast for 3 h was determined in normal mice. We used roflumilast, a selective PDE4 inhibitor and bronchodilator for severe COPD approved by the US Food and Drug Administration, as a reference drug. In the results, HTA (100 μmol/kg, p.o.) or roflumilast (5 mg/kg, p.o.) significantly suppressed all R L values of MCh at 0.78 ~ 25 mg/mL and enhanced C dyn values of MCh at 3.125 ~ 25 mg/mL compared to OVA-sensitized and -challenged control mice. Orally administered 1, 3 or 10 mg/kg roflumilast

The engagement of oral-associated lymphoid tissues during oral versus gastric antigen administration.

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Bankvall, Maria; Östberg, Anna-Karin; Jontell, Mats; Wold, Agnes; Östman, Sofia

2016-09-01

The role of oral-associated lymphoid tissues during induction of oral tolerance still remains elusive. Therefore, the aim was to compare T-cell activation and induction of tolerance to ovalbumin (OVA) presented through either of two routes; deposited into the oral cavity, or the stomach, thereby bypassing the oral cavity. OVA was administered by the oral or gastric route to BALB/c mice that had received OVA-specific DO11.10+ CD4(+) T cells, stained with CellTrace(™) Violet dye, through intravenous injection. Proliferating OVA-specific T cells were detected in the nose-associated lymphoid tissues (NALT) and the cervical, mesenteric and peripheral lymph nodes at different time-points following OVA exposure. OVA-specific T-cell proliferation was initially observed in the NALT 1 hr after oral, but not gastric, administration. However, at day 1, proliferation at this site was also detected after gastric administration and profound proliferation was observed at all sites by day 4. For the oral route the degree of proliferation observed was lower in the peripheral lymph nodes by day 4 compared with the other sites. These results demonstrate a similar activation pattern achieved by the two routes. However, the NALT distinguishes itself as a site of rapid T-cell activation towards fed antigens irrespective of feeding regimen. To evaluate induction of tolerance a semi-effective OVA dose was used, to detect differences in the degree of tolerance achieved. This was performed in a model of OVA-induced airway hypersensitivity. No differences in tolerance induction were observed between the two administration routes. © 2016 John Wiley & Sons Ltd.

Loss of sialic acid binding domain redirects protein σ1 to enhance M cell-directed vaccination.

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Dagmara Zlotkowska

Full Text Available Ovalbumin (OVA genetically fused to protein sigma 1 (pσ1 results in tolerance to both OVA and pσ1. Pσ1 binds in a multi-step fashion, involving both protein- and carbohydrate-based receptors. To assess the relative pσ1 components responsible for inducing tolerance and the importance of its sialic binding domain (SABD for immunization, modified OVA-pσ1, termed OVA-pσ1(short, was deleted of its SABD, but with its M cell targeting moiety intact, and was found to be immunostimulatory and enhanced CD4(+ and CD8(+ T cell proliferation. When used to nasally immunize mice given with and without cholera toxin (CT adjuvant, elevated SIgA and serum IgG responses were induced, and OVA-pσ1(s was more efficient for immunization than native OVA+CT. The immune antibodies (Abs were derived from elevated Ab-forming cells in the upper respiratory tissues and submaxillary glands and were supported by mixed Th cell responses. Thus, these studies show that pσ1(s can be fused to vaccines to effectively elicit improved SIgA responses.

An essential regulatory role of downstream of kinase-1 in the ovalbumin-induced murine model of asthma.

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Chang-Min Lee

Full Text Available The downstream of kinase (DOK-1 is involved in the protein tyrosine kinase (PTK pathway in mast cells, but the role of DOK-1 in the pathogenesis of asthma has not been defined. In this study, we have demonstrated a novel regulatory role of DOK-1 in airway inflammation and physiologic responses in a murine model of asthma using lentiviral vector containing DOK-1 cDNA or DOK-1-specific ShRNA. The OVA-induced inflammatory cells, airway hyperresponsiveness, Th2 cytokine expression, and mucus response were significantly reduced in DOK-1 overexpressing mice compared to OVA-challenged control mice. The transgenic introduction of DOK-1 significantly stimulated the activation and expression of STAT-4 and T-bet, while impressively inhibiting the activation and expression of STAT-6 and GATA-3 in airway epithelial cells. On the other hand, DOK-1 knockdown mice enhanced STAT-6 expression and its nuclear translocation compared to OVA-challenged control mice. When viewed in combination, our studies demonstrate DOK-1 regulates allergen-induced Th2 immune responses by selective stimulation and inhibition of STAT-4 and STAT-6 signaling pathways, respectively. These studies provide a novel insight on the regulatory role of DOK-1 in allergen-induced Th2 inflammation and airway responses, which has therapeutic potential for asthma and other allergic diseases.

CCR9 Is Not Required for the Homing of Pro-inflammatory Effector T cells, but Is Crucial for Recruitment and Expansion of FoxP3+ CD8+ Tregs in the Small Intestine

DEFF Research Database (Denmark)

Gomez-Casado, Cristina; Joeris, Thorsten; Holmkvist, Petra

Chemokine receptor 9 (CCR9) is required for the homeostatic recruitment of T cells to the mucosa of the small intestine. Accordingly, CCR9 has been suggested as a potential target to inhibit the recruitment of proinflammatory effector T cells (Teff) in inflammatory bowel disease (IBD). Since...... the contribution of CCR9 to the recruitment of Teff in inflammation is not entirely clear, we aimed to address this question using IFABPtOva mice. These mice express Ovalbumin (Ova) specifically in small intestinal epithelial cells, which allows triggering of acute inflammation following transfer of Ova......-specific CD8+ T cells (OT-I cells) and adjuvant treatment. Strikingly, intestinal inflammation in IFABP-tOva mice could also be triggered following transfer of CCR9-deficient OT-I cells, demonstrating that CCR9 is not required for homing of Teff cells. Interestingly, OTI cells transferred to IFABP-tOva mice...

Schistosoma mansoni Phosphoenolpyruvate Carboxykinase, a Novel Egg Antigen: Immunological Properties of the Recombinant Protein and Identification of a T-Cell Epitope

OpenAIRE

Asahi, Hiroko; Osman, Ahmed; Cook, Rosemary M.; LoVerde, Philip T.; Stadecker, Miguel J.

2000-01-01

In schistosomiasis mansoni, hepatic granulomatous inflammation surrounding parasite eggs is mediated by CD4+ T helper (Th) cells sensitized to schistosomal egg antigens (SEA). We previously showed that a prominent lymphoproliferative response of CD4+ Th cells from schistosome-infected C57BL/6 (BL/6) mice was directed against a 62-kDa component of SEA. A partial amino acid sequence of the 62-kDa component was found to be identical with one present in the enzyme phosphoenolpyruvate carboxykinas...

[Impact of ecological protection construction on schistosomiasis transmission of Qionghai Lake wetland in Xichang City].

Science.gov (United States)

Feng, Zong-liang; Xu, Cong-min; Yin, Hong-zhi; Hua, Jiao; Lai, Yu-hua; Zhao, Lin; Wu, Zhong-ping

2016-02-01

To understand the impact of Qionghai Lake wetland ecological protection construction on the prevalence of schistosomiasis, so as to provide the evidence for formulating the strategies for schistosomiasis control and prevention. A retrospective survey of the construction of Qionghai Lake wetland was performed, and eleven villages around the wetland were surveyed for schistosomiasis endemic situation. The influence of the wetland project on the schistosomiasis prevalence and Oncomelania hupensis snail status were investigated. Before the construction of Qionghai Lake wetland, the snail elimination and extended chemotherapy for residents was performed. After the project was finished, the roads and ditches were hardened. From 2009 to 2014, the schistosome infection rate of residents declined from 0.37% to 0. No schistosome infected snails were found and in recent 2 years, no snails were found. No mice were infected in the sentinel tests. The construction of Qionghai Lake wetland effectively eliminates snails, and interrupts the transmission of schistosomiasis. However, the environment of the wetland is more suitable for snail breeding, and therefore, the surveillance still should be strengthened.

Experimental chemotherapy of Schistosomiasis III: laboratory and clinical trials with trichlorphone, an organophosphorus compound

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Naftale Katz

1968-10-01

Full Text Available Oogram studies have been carried out on mice, hamsters, and Cebus morikeys experimentally infected with Schistosoma mansoni and treated with trichlorphone (0,0-dimethyl 1-hydroxy-2, 2, 2-trichloroethylphosphonate. In mice, despite a slight hepatic shift of schistosomes, all animais presented oogram changes when dosed, per os, at the schedules of 200, and 100 mg/kg/day × 7. In hamsters, antischistosomal activity could be detected only at toxic leveis. In monkeys, trichlorphone showed insignificant action even after oral administration of 30 mg/kg/day for 10 consecutive days. In 5 volunteers, a sharp drop in cholinesterase plasma level was observed 24 hours after a single oral dose of 7.5 mg/kg. However, cholinesterase levels returned to the initial values within a period of 11 to 27 days. Trichlorphone was then administered to 12 schistosome patients (7.5 mg/kg/day, every fort- night, × 5. One month after therapy, interruption of egg laying was observed in 6 patients. Late parasitological control showed that all treated patients continued to pass viable S. mansoni eggs with their stools.

An assessment of anti-schistosomal treatment on physical work capacity.

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Awad El Karim, M A; Collins, K J; Sukkar, M Y; Omer, A H; Amin, M A; Doré, C

1981-04-01

Acting as their own controls, village subjects from the Gezira are of the Sudan with relatively high levels of schistosomiasis infection were first tested in an exercise laboratory in Khartoum and the tests were then repeated after a period of about 1 yr during which time the subjects were treated with hycanthone and periodically monitored to ensure that they had remained free of the disease. In the meantime they were also given anti-malarial prophylaxis. Laboratory tests showed a significant improvement in physiological work capacity of up to 20% after treatment compared with untreated controls. An overall improvement in pulmonary function, particularly forced vital capacity, was observed as well as a significant increase in mean haemoglobin concentration by 1.1 g/100 ml of blood in the treated group. Apart from these improvements in physical working capacity, the treated subjects subjectively felt better after the exercise tests, as expressed by the disappearance of fatiguability.

Agrochemicals increase risk of human schistosomiasis by supporting higher densities of intermediate hosts.

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Halstead, Neal T; Hoover, Christopher M; Arakala, Arathi; Civitello, David J; De Leo, Giulio A; Gambhir, Manoj; Johnson, Steve A; Jouanard, Nicolas; Loerns, Kristin A; McMahon, Taegan A; Ndione, Raphael A; Nguyen, Karena; Raffel, Thomas R; Remais, Justin V; Riveau, Gilles; Sokolow, Susanne H; Rohr, Jason R

2018-02-26

Schistosomiasis is a snail-borne parasitic disease that ranks among the most important water-based diseases of humans in developing countries. Increased prevalence and spread of human schistosomiasis to non-endemic areas has been consistently linked with water resource management related to agricultural expansion. However, the role of agrochemical pollution in human schistosome transmission remains unexplored, despite strong evidence of agrochemicals increasing snail-borne diseases of wildlife and a projected 2- to 5-fold increase in global agrochemical use by 2050. Using a field mesocosm experiment, we show that environmentally relevant concentrations of fertilizer, a herbicide, and an insecticide, individually and as mixtures, increase densities of schistosome-infected snails by increasing the algae snails eat and decreasing densities of snail predators. Epidemiological models indicate that these agrochemical effects can increase transmission of schistosomes. Identifying agricultural practices or agrochemicals that minimize disease risk will be critical to meeting growing food demands while improving human wellbeing.

[Imiquimod combined with dendritic cell vaccine decreases Treg proportion and enhances anti-tumor responses in mice bearing melanoma].

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Ren, Shurong; Wang, Qiubo; Zhang, Yanli; Lu, Cuixiu; Li, Ping; Li, Yumei

2017-02-01

Objective To investigate the therapeutic effect of Toll-like receptor 7 (TLR7) agonist imiquimod combined with dendritic cell (DC)-based tumor vaccine on melanoma in mice and the potential mechanism. Methods Melanoma-bearing mouse models were established by subcutanous injection of B16-OVA cells into C57BL/6 mice. DCs were isolated from mouse bone marrow and propagated in culture medium with recombinant mouse granulocyte-macrophage colony-stimulating factor (rmGM-CSF) and recombinant mouse interleukin-4 (rmIL-4). DC vaccine (OVA-DC) was prepared by overnight incubation of DCs added with chicken ovalbumin. C57BL/6 mice were separated into four groups which were treated with PBS, topical imiquimod application, OVA-DC intradermal injection and imiquimod plus OVA-DC, respectively. The tumor size was calculated by digital vernier caliper. Peripheral blood CD4 + FOXP3 + Tregs of the tumor-bearing mice was detected by flow cytometry. The cytotoxicity of splenic lymphocyte against B16-OVA was assessed in vitro by CCK-8 assay. Results Compared with the other three groups, B16-OVA-bearing mice treated with imiquimod plus DC vaccine had the smallest tumor volume. The percentage of CD4 + FOXP3 + Tregs decreased significantly in the combined treated mice. The combined treatment enhanced significantly cytotoxicity of splenic lymphocytes against B16-OVA cells. Conclusion Imiquimod combined with antigen-pulsed-DC vaccine could reduce CD4 + FOXP3 + Treg proportion and promote anti-tumor effect in mice with melanoma.

Immune adjuvant activity of the olive, soybean and corn oils

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Ana Claudia Marinho da Silva

2016-08-01

Full Text Available In the last half of the century, a large amount of substances has been used as immune adjuvant. The immune adjuvant effect of olive, soybean and corn oils in Swiss mice immunized with ovalbumin (OVA plus aluminum hydroxide or emulsified in Marcol, soybean, olive or corn oils was evaluated through the OVA-specific antibodies determined by ELISA and Passive Cutaneous Anaphylaxis. In this work the comparison of the intensity of the immune response was established by the Bayesian analysis. The adjuvant effect of the vegetable oils was shown to be more effective than aluminium hydroxide. Regarding to OVA-specific IgE synthesis, olive oil had the slowest adjuvant effect of the three vegetable oils. Accordingly, olive oil was the most convenient among the vegetable oils to be used as immune adjuvant, since it stimulated a higher production of OVA-specific Ig and lower levels of anti-OVA IgE.

Augmentation of antigen-specific immune responses using DNA-fusogenic liposome vaccine

International Nuclear Information System (INIS)

Yoshikawa, Tomoaki; Imazu, Susumu; Gao Jianqing; Hayashi, Kazuyuki; Tsuda, Yasuhiro; Shimokawa, Mariko; Sugita, Toshiki; Niwa, Takako; Oda, Atushi; Akashi, Mitsuru; Tsutsumi, Yasuo; Mayumi, Tadanori; Nakagawa, Shinsaku

2004-01-01

In an attempt to enhance the immunological efficacy of genetic immunization, we investigated a new biological means for delivering antigen gene directly to the cytoplasm via membrane fusion. In this context, we investigated fusogenic liposome (FL) encapsulating DNA as a possible genetic immunization vehicle. RT-PCR analysis indicated that a FL could introduce and express encapsulating OVA gene efficiently and rapidly in vitro. Consistent with this observation, an in vitro assay showed that FL-mediated antigen-gene delivery can induce potent presentation of antigen via the MHC class I-dependent pathway. Accordingly, immunization with FL containing the OVA-gene induced potent OVA-specific Th1 and Th2 cytokine production. Additionally, OVA-specific CTL responses and antibody production were also observed in systemic compartments including the spleen, upon immunization with the OVA-gene encapsulating FL. These findings suggest that FL is an effective genetic immunization carrier system for the stimulation of antigen-specific immune responses against its encoding antigen

Oral treatment with enrofloxacin early in life promotes Th2-mediated immune response in mice.

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Strzępa, Anna; Majewska-Szczepanik, Monika; Kowalczyk, Paulina; Woźniak, Dorota; Motyl, Sylwia; Szczepanik, Marian

2016-02-01

Th2 lymphocytes play a crucial role in the development of allergy. These pathologies are caused by coordinated production of the cytokines IL-4, IL-5 and IL-13 that regulate the activity of eosinophils, basophils and B cells. According to the 'hygiene hypothesis', the reduced exposure to microorganisms favors allergy occurrence. The advances in medicine in the field of infection therapy promoted an increasing application of antibiotics which, apart from eliminating pathogens, also partially eliminate the microbiota. Epicutaneous (EC) immunization with ovalbumin (OVA) followed by OVA challenge was used to study the influence of partial gut flora depletion by oral treatment with enrofloxacin on type-2 immune response. Current work describes the influence of enrofloxacin application on anti-OVA antibody production and cytokine synthesis in young and adult mice. Immune response in adult mice is less sensitive to modification of natural gut flora. We observed that enrofloxacin treatment of adult mice leads to significant decrease of anti-OVA IgG2a production while synthesis of anti-OVA IgE was not changed. The production of type-1 (IFN-γ), type-2 (IL-4, IL-5, IL-10, IL-13) and Th17-associated (IL-17A) cytokines was inhibited. On the other hand, treatment of young mice with enrofloxacin significantly upregulates the production of anti-OVA IgE and inhibits the secretion of anti-OVA IgG2a antibodies. Additionally, treatment with enrofloxacin early in life prior to OVA immunization results in increased production of type-2 (IL-4, IL-10 and IL-13) cytokines. Our results clearly indicate that the immune system is more vulnerable to decreased bacterial exposure early in life that may promote development of allergy. Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Artificially synthesized helper/killer-hybrid epitope long peptide (H/K-HELP): preparation and immunological analysis of vaccine efficacy.

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Masuko, Kazutaka; Wakita, Daiko; Togashi, Yuji; Kita, Toshiyuki; Kitamura, Hidemitsu; Nishimura, Takashi

2015-01-01

To elucidate the immunologic mechanisms of artificially synthesized helper/killer-hybrid epitope long peptide (H/K-HELP), which indicated a great vaccine efficacy in human cancers, we prepared ovalbumin (OVA)-H/K-HELP by conjugating killer and helper epitopes of OVA-model tumor antigen via a glycine-linker. Vaccination of C57BL/6 mice with OVA-H/K-HELP (30 amino acids) but not with short peptides mixture of class I-binding peptide (8 amino-acids) and class II-binding peptide (17 amino-acids) combined with adjuvant CpG-ODN (cytosine-phosphorothioate-guanine oligodeoxynucleotides), induced higher numbers of OVA-tetramer-positive CTL with concomitant activation of IFN-γ-producing CD4(+) Th1 cells. However, replacement of glycine-linker of OVA-H/K-HELP with other peptide-linker caused a significant decrease of vaccine efficacy of OVA-H/K-HELP. In combination with adjuvant CpG-ODN, OVA-H/KHELP exhibited greater vaccine efficacy compared with short peptides vaccine, in both preventive and therapeutic vaccine models against OVA-expressing EG-7 tumor. The elevated vaccine efficacy of OVAH/K-HELP might be derived from the following mechanisms: (i) selective presentation by only professional dendritic cells (DC) in vaccinated draining lymph node (dLN); (ii) a long-term sustained antigen presentation exerted by DC to stimulate both CTL and Th1 cells; (iii) formation of three cells interaction among DC, Th and CTL. In comparative study, H/K-HELP indicated stronger therapeutic vaccine efficacy compared with that of extended class I synthetic long peptide, indicating that both the length of peptide and the presence of Th epitope peptide were crucial aspects for preparing artificially synthesized H/K-HELP vaccine. Copyright © 2014 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

The effects of ovalbumin as a protein source during the in vitro production of bovine embryos

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Tatiane Almeida Drummond Tetzner

2011-10-01

Full Text Available Embryo quality is influenced by the culture conditions that affect in vitro maturation (IVM, fertilization (IVF and culture (IVC rates. The present study investigated the feasibility of producing bovine embryos after the replacement of fetal calf serum (FCS and bovine serum albumin (BSA by ovalbumin (OVA. The IVM and IVC medium were supplemented with 10% FCS, 4 mg/mL BSA, or 4 mg/mL OVA. The IVF medium was supplemented with 6 mg/mL BSA or OVA. For IVM, supplementation with FCS, BSA, and OVA did not affect nuclear maturation or cortical granule migration. Higher rates of formation of two pronuclei were obtained when FCS was employed for IVM (79.97%, regardless of the supplement used for IVF, and when BSA was used for IVF (59.4%, regardless of the supplement used for IVM. Supplementation with OVA for IVM+IVC (20.40% and for IVF (22.15% was inferior to supplementation with FCS for IVM+IVC (30.47% and with BSA for IVF (28.91% for blastocyst development. Hatching rates were lower using OVA for IVM+IVC (23.02% and for IVF (28.93% compared with FCS and BSA under the same conditions (40.78 and 34.82%, respectively and BSA for IVF (36.82%. Supplementation with OVA for IVM+IVC and IVF resulted in reduced inner cell mass, trophectoderm cells and total blastocyst cell numbers (17.29, 37.88, and 55.17, respectively. In conclusion, OVA is a protein source for bovine in vitro embryo production, although the quantity and quality of bovine blastocysts using only ovalbumin in the entire in vitro production process are lower than those obtained in the presence of FCS and BSA, when used as supplements in any step of bovine in vitro embryo production.

Fabrication of micromagnetic beads with molecular recognition/electron-transfer peptides for the sensing of ovalbumin

Energy Technology Data Exchange (ETDEWEB)

Sugawara, Kazuharu, E-mail: kzsuga@maebashi-it.ac.jp [Maebashi Institute of Technology, Gunma, 371-0816 (Japan); Kuramitz, Hideki [Department of Environmental Biology and Chemistry, Graduate School of Science and Engineering for Research, University of Toyama, Toyama, 930-8555 (Japan); Shinohara, Hiroki [Maebashi Institute of Technology, Gunma, 371-0816 (Japan)

2017-03-15

Electrochemical sensing of ovalbumin (OVA) was performed using magnetic beads with OVA recognition (RNRCKGTDVQAW)/electron-transfer (YYYYC) peptides. The focus of this study was to construct a highly sensitive and regenerative tool for OVA detection based on the interaction between a protein and peptide-1(RNRCKGTDVQAWYYYYC). The peptide-1 was introduced to the bead through four types of cross-linking reagents. Magnetic beads of different sizes with N-(6-maleimidocaproyloxy)sulfosuccinimide (Sulfo-EMCS) were also prepared. An oxidation peak due to tyrosine residues at 0.65 V depended on the distance of the electron-transfer peptide from the bead surface and on the surface area of the magnetic beads that contacted the electrode surface. The response of the electro-transfer peptide moiety was decreased because the protein was accumulated via the recognition peptide on the beads. When using Sulfo-EMCS and beads that were 6.0–6.9 μm in diameter, the calibration curve of OVA was linear and ranged from 8.0 × 10{sup −13} to 2.0 × 10{sup −11} M. To regenerate the magnetic beads, the measurements were achieved after removal of the OVA using a denaturing reagent. When OVA was added to fetal bovine serum containing a complex matrix, OVA was recovered at a rate of 98–100%. Consequently, these magnetic beads could be a powerful tool for the sensing of OVA in real samples. - Highlights: • Ovalbumin recognition/electron-transfer peptides were immobilized on magnetic beads. • The accumulation of the protein through the peptides on the beads caused the change of electrode response. • The magnetic beads could be reused for sensing of ovalbumin.

Effect of the Velvet Antler of Formosan Sambar Deer (Cervus unicolor swinhoei on the Prevention of an Allergic Airway Response in Mice

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Ching-Yun Kuo

2012-01-01

Full Text Available Two mouse models were used to assay the antiallergic effects of the velvet antler (VA of Formosan sambar deer (Cervus unicolor swinhoei in this study. The results using the ovalbumin- (OVA- sensitized mouse model showed that the levels of total IgE and OVA-specific IgE were reduced after VA powder was administrated for 4 weeks. In addition, the ex vivo results indicated that the secretion of T helper cell 1 (Th1, regulatory T (Treg, and Th17 cytokines by splenocytes was significantly increased (P<0.05 when VA powder was administered to the mice. Furthermore, OVA-allergic asthma mice that have been orally administrated with VA powder showed a strong inhibition of Th2 cytokine and proinflammatory cytokine production in bronchoalveolar fluid compared to control mice. An increase in the regulatory T-cell population of splenocytes in the allergic asthma mice after oral administration of VA was also observed. All the features of the asthmatic phenotype, including airway inflammation and the development of airway hyperresponsiveness, were reduced by treatment with VA. These findings support the hypothesis that oral feeding of VA may be an effective way of alleviating asthmatic symptoms in humans.

Medicinal plants effectiveness against helminths of cattle

African Journals Online (AJOL)

SARAH

2015-02-28

Feb 28, 2015 ... plants stored in concentrations of 25%, 50%, 75% and the system maintained at time schedules of 2h, 4h and. 8h. Control .... Number of distorted ova/adult per field x 100 .... methods, a guide to modern techniques of plant.

Genetic variation and differentiation of three Schistosoma species from the Philippines, Laos, and Peninsular Malaysia.

Science.gov (United States)

Woodruff, D S; Merenlender, A M; Upatham, E S; Viyanant, V

1987-03-01

Electrophoretically-detected allozyme variation is described in strains of Schistosoma japonicum (4 Philippine strains), S. mekongi (Laos), and an undescribed anthropophilic S. japonicum-like schistosome from Peninsular Malaysia. Result, together with those reported previously for 8 other strains (S. japonicum, China, Formosa, Japan, Philippines; S. mekongi, 2 substrains; Malaysian schistosome, 2 strains) permit a composite genetic characterization of 15 strains of Asian schistosomes at 9-18 presumptive loci. The proportion of polymorphic loci (P) and the mean heterozygosity per locus (H) were zero in all strains. Although this was expected for strains that had been in laboratory culture for up to 50 years, we expected to detect variation in strains based on 10-50 recently field-collected infected snails. We expected S. japonicum to be as variable as S. mansoni (P = 0.13 (0-0.33), H = 0.04, 18 loci, 22 strains) as it is believed to reproduce sexually, has an evolutionary history of several million years, inhabits a wide geographic range, coevolved with a genetically variable intermediate snail host, and has a diversity of mammalian hosts. No differences were detected between the 5 S. japonicum strains from Leyte and Luzon (Philippines), between the 3 S. mekongi strains, or between the 3 Malaysian schistosome strains; these groups and the remaining S. japonicum strains representing Mindoro (Philippines), China, Formosa, and Japan each have distinctive multilocus electromorphic patterns. Nei's genetic distances (D) were calculated to estimate interstrain and interspecific divergence. Interstrain genetic distances in S. japonicum averaged greater than 0.3; much higher than those reported previously for S. mansoni (D = 0.06, D(max) = 0.24). S. japonicum (Mindoro) was moderately differentiated from the Leyte-Luzon strains (D = 0.29, 12 loci). Estimates of the S. japonicum China-Philippine distance (D greater than 0.4, 11 loci) are high for conspecific populations and

Comparison of worm development and host immune responses in natural hosts of schistosoma japonicum, yellow cattle and water buffalo

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Yang Jianmei

2012-03-01

Full Text Available Abstract Background Yellow cattle and water buffalo are two of the most important natural hosts for Schistosoma japonicum in China. Previous observation has revealed that yellow cattle are more suited to the development of S. japonicum than water buffalo. Understanding more about the molecular mechanisms involved in worm development, as well as the pathological and immunological differences between yellow cattle and water buffalo post infection with S japonicum will provide useful information for the vaccine design and its delivery procedure. Results The worm length (p p p + T cells was higher in yellow cattle, while the percentage of CD8+ T cells was higher in water buffalo from pre-infection to 7 w post infection. The CD4/CD8 ratios were decreased in both species after challenge with schistosomes. Comparing with water buffalo, the IFN-γ level was higher and decreased significantly, while the IL-4 level was lower and increased gradually in yellow cattle from pre-infection to 7 w post infection. Conclusions In this study, we confirmed that yellow cattle were more suited to the development of S. japonicum than water buffalo, and more serious pathological damage was observed in infected yellow cattle. Immunological analysis suggested that CD4+ T cells might be an integral component of the immune response and might associate with worm development in yellow cattle. A shift from Th1 to Th2 type polarized immunity was only shown clearly in schistosome-infected yellow cattle, but no shift in water buffalo. The results provide valuable information for increased understanding of host-schistosome interactions, and for control of schistosomiasis.

Effect of the anti-IL-17 antibody on allergic inflammation in an obesity-related asthma model.

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Liang, Lin; Hur, Jung; Kang, Ji Young; Rhee, Chin Kook; Kim, Young Kyoon; Lee, Sook Young

2018-04-19

The co-occurrence of obesity aggravates asthma symptoms. Diet-induced obesity increases helper T cell (TH) 17 cell differentiation in adipose tissue and the spleen. The 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor pravastatin can potentially be used to treat asthma in obese patients by inhibiting interleukin 17 (IL-17) expression. This study investigated the combined effects of pravastatin and anti-IL-17 antibody treatment on allergic inflammation in a mouse model of obesity-related asthma. High-fat diet (HFD)-induced obesity was induced in C57BL/6 mice with or without ovalbumin (OVA) sensitization and challenge. Mice were administered the anti-IL-17 antibody, pravastatin, or both, and pathophysiological and immunological responses were analyzed. HFD exacerbated allergic airway inflammation in the bronchoalveolar lavage fluid of HFD-OVA mice as compared to OVA mice. Blockading of the IL-17 in the HFD-OVA mice decreased airway hyper-responsiveness (AHR) and airway inflammation compared to the HFD-OVA mice. Moreover, the administration of the anti-IL-17 antibody decreased the leptin/adiponectin ratio in the HFD-OVA but not the OVA mice. Co-administration of pravastatin and anti-IL-17 inhibited airway inflammation and AHR, decreased goblet cell numbers, and increased adipokine levels in obese asthmatic mice. These results suggest that the IL-17-leptin/adiponectin axis plays a key role in airway inflammation in obesity-related asthma. Our findings suggest a potential new treatment for IL-17 as a target that may benefit obesity-related asthma patients who respond poorly to typical asthma medications.

Low-molecular-weight polysaccharides from Agaricus blazei Murrill modulate the Th1 response in cancer immunity

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Jiang, Liyan; Yu, Zhipu; Lin, Yu; Cui, Liran; Yao, Shujuan; Lv, Liyan; Liu, Jicheng

2018-01-01

To assess the effect of low-molecular-weight polysaccharides from Agaricus blazei Murrill (ABP-AW1) as an immunoadjuvant therapy for type 1 T-helper (Th1) responses in tumorigenesis, C57BL/6 mice were inoculated subcutaneously with ovalbumin (E.G7-OVA). After 3, 10 and 17 days, the mice were immunized with PBS, OVA alone, or OVA and ABP-AW1, at low (50 µg), intermediate (100 µg) or high (200 µg) doses. Tumor growth was examined and compared among the groups, as were the following parameters: Splenocyte viability/proliferation, peripheral blood CD4+/CD8+ T cell ratio, serum OVA-specific IgG1 and IgG2b, secretion of interleukin (IL)-2 and interferon (IFN)-γ, and IFN-γ production on a single cell level from cultured splenocytes. Tumor growth in mice treated with OVA and ABP-AW1 (100 or 200 µg) was significantly slower, compared with in the other groups at the same time-points. OVA with 100 or 200 µg ABP-AW1 was associated with a higher number of total splenocytes, a higher ratio of peripheral blood CD4+/CD8+ T-lymphocytes, higher serum levels of OVA-specific Th1-type antibody IgG2b and greater secretion of the Th1 cytokines IL-1 and IFN-γ from splenocytes. ABP-AW1 is a promising immunoadjuvant therapy candidate, due to its ability to boost the Th1 immune response when co-administered with a cancer vaccine intended to inhibit cancer progression. PMID:29467867

Elimination of Schistosoma mansoni in infected mice by slow release of artemisone

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Daniel Gold

2017-08-01

Full Text Available The current treatment of schistosomiasis is based on the anti-helminthic drug praziquantel (PZQ. PZQ affects only the adult stages of schistosomes. In addition, resistance to PZQ is emerging. We suggest a drug, which could serve as a potential alternative or complement to PZQ, and as a means of treating infections at earlier, pre-granuloma stage. Derivatives of the peroxidic antimalarial drug artemisinin have been indicated as alternatives, because both plasmodia and schistosomes are blood-feeding parasites. The mechanism of action of artemisinins is related to oxidative effects of the artemisinins on intracellular reductants leading to formation of cytotoxic reactive oxygen species. We used artemisone, which has improved pharmacokinetics and anti-plasmodial activity, and reduced toxicity compared to other artemisinins in clinical use against malaria. We infected adult mice by subcutaneous injection of S. mansoni cercariae (about 200 and treated them at various times post infection by the following methods: i. artemisone suspension administered by gavage (400–450 mg/kg; ii. subcutaneous injection of a gel containing a known concentration of artemisone (115–120 mg/kg; iii. subcutaneous insertion of the drug incorporated in a solid polymer (56–60 mg/kg; iv. intraperitoneal injection of the drug solubilized in DMSO (115–120 mg/kg. Drug administration in polymers was performed to enable slow release of the artemisone that was verified in vivo and in vitro bioassays using drug-sensitive malaria parasites. We found superior strong anti-schistosome effects up to a total reduction of worm number, mainly following repetitive treatments with the drug absorbed in the polymers (73.1% and 95.9% reduction in mice treated with artemisone in gel 7 and 14, and 21, 28 and 35 days post infection, respectively. The results indicate that artemisone has a potent anti-schistosome activity. Its main importance in this context is its effectiveness in

The concentration of kynurenine in rat model of asthma.

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Barbara Mroczko

2008-06-01

Full Text Available Asthma is a chronic inflammatory disease that involves the immune system activation. Evidence is accumulating about the role of kynurenine pathway in the immune system regulation. The kynurenine pathway includes several metabolites of tryptophan, among others kynurenine (KYN. To study the immunological system regulation in asthma a simple and sensitive models of asthma are required. In the present study we induced rat model of asthma using ovalbumin (OVA sensitization followed by challenge with OVA. The development of asthma has been confirmed by plasma total IgE measurement and the histological examination. The concentration of KYN has been determined in plasma, lungs and liver by high-performance liquid chromatography (HPLC. In OVA sensitized rats the concentration of total IgE was statistically significantly increased as compared to VEH sensitized control groups (437.6 +/- 97.7 kU/l vs 159.2 +/- 22.7 kU/l, respectively; p< 0.01. In asthmatic animals, the number of eosinophils, neutrophils and mast cells increased considerably, and epithelial lesion and the increase in airway epithelium goblet cells and edema of bronchial mucosa were present. We did not observe any significant changes in the concentration of KYN in plasma, lungs or liver between studied groups. In conclusion, the concentration of KYN remains unchanged in asthmatic animals as compared to control groups. Further studies using rat model of asthma are warranted to establish the role of kynurenine pathway regulation in asthma.

Adverse effect of nano-silicon dioxide on lung function of rats with or without ovalbumin immunization.

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Bing Han

Full Text Available BACKGROUND: The great advances of nanomaterials have brought out broad important applications, but their possible nanotoxicity and risks have not been fully understood. It is confirmed that exposure of environmental particulate matter (PM, especially ultrafine PM, are responsible for many lung function impairment and exacerbation of pre-existing lung diseases. However, the adverse effect of nanoparticles on allergic asthma is seldom investigated and the mechanism remains undefined. For the first time, this work investigates the relationship between allergic asthma and nanosized silicon dioxide (nano-SiO₂. METHODOLOGY/PRINCIPAL FINDINGS: Ovalbumin (OVA-treated and saline-treated control rats were daily intratracheally administered 0.1 ml of 0, 40 and 80 µg/ml nano-SiO₂ solutions, respectively for 30 days. Increased nano-SiO₂ exposure results in adverse changes on inspiratory and expiratory resistance (Ri and Re, but shows insignificant effect on rat lung dynamic compliance (Cldyn. Lung histological observation reveals obvious airway remodeling in 80 µg/ml nano-SiO₂-introduced saline and OVA groups, but the latter is worse. Additionally, increased nano-SiO₂ exposure also leads to more severe inflammation. With increasing nano-SiO₂ exposure, IL-4 in lung homogenate increases and IFN-γ shows a reverse but insignificant change. Moreover, at a same nano-SiO₂ exposure concentration, OVA-treated rats exhibit higher (significant IL-4 and lower (not significant IFN-γ compared with the saline-treated rats. The percentages of eosinophil display an unexpected result, in which higher exposure results lower eosinophil percentages. CONCLUSIONS/SIGNIFICANCE: This was a preliminary study which for the first time involved the effect of nano-SiO₂ to OVA induced rat asthma model. The results suggested that intratracheal administration of nano-SiO₂ could lead to the airway hyperresponsiveness (AHR and the airway remolding with or without OVA

Effect of lipoarabinomannan from Mycobacterium avium subsp avium in Freund's incomplete adjuvant on the immune response of cattle.

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Colavecchia, S B; Jolly, A; Fernández, B; Fontanals, A M; Fernández, E; Mundo, S L

2012-02-01

The aim of the present study was to determine whether lipoarabinomannan (LAM), in combination with Freund's incomplete adjuvant (FIA), was able to improve cell-mediated and antibody-mediated immune responses against ovalbumin (OVA) in cattle. Twenty-three calves were assigned to four treatment groups, which were subcutaneously immunized with either OVA plus FIA, OVA plus FIA and LAM from Mycobacterium avium subsp avium, FIA plus LAM, or FIA alone. Lymphoproliferation, IFN-γ production and cell subpopulations on peripheral blood mononuclear cells before and 15 days after treatment were evaluated. Delayed hypersensitivity was evaluated on day 57. Specific humoral immune response was measured by ELISA. Inoculation with LAM induced higher levels of lymphoproliferation and IFN-γ production in response to ConA and OVA (P < 0.05). Specific antibody titers were similar in both OVA-immunized groups. Interestingly, our results showed that the use of LAM in vaccine preparations improved specific cell immune response evaluated by lymphoproliferation and IFN-γ production by at least 50 and 25%, respectively, in cattle without interfering with tuberculosis and paratuberculosis diagnosis.

The C5a/C5aR1 axis controls the development of experimental allergic asthma independent of LysM-expressing pulmonary immune cells.

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Anna V Wiese

Full Text Available C5a regulates the development of maladaptive immune responses in allergic asthma mainly through the activation of C5a receptor 1 (C5aR1. Yet, the cell types and the mechanisms underlying this regulation are ill-defined. Recently, we described increased C5aR1 expression in lung tissue eosinophils but decreased expression in airway and pulmonary macrophages as well as in pulmonary CD11b+ conventional dendritic cells (cDCs and monocyte-derived DCs (moDCs during the allergic effector phase using a floxed green fluorescent protein (GFP-C5aR1 knock-in mouse. Here, we determined the role of C5aR1 signaling in neutrophils, moDCs and macrophages for the pulmonary recruitment of such cells and the importance of C5aR1-mediated activation of LysM-expressing cells for the development of allergic asthma. We used LysM-C5aR1 KO mice with a specific deletion of C5aR1 in LysMCre-expressing cells and confirmed the specific deletion of C5aR1 in neutrophils, macrophages and moDCs in the airways and/or the lung tissue. We found that alveolar macrophage numbers were significantly increased in LysM-C5aR1 KO mice. Induction of ovalbumin (OVA-driven experimental allergic asthma in GFP-C5aR1fl/fl and LysM-C5aR1 KO mice resulted in strong but similar airway resistance, mucus production and Th2/Th17 cytokine production. In contrast, the number of airway but not of pulmonary neutrophils was lower in LysM-C5aR1 KO as compared with GFP-C5aR1fl/fl mice. The recruitment of macrophages, cDCs, moDCs, T cells and type 2 innate lymphoid cells was not altered in LysM-C5aR1 KO mice. Our findings demonstrate that C5aR1 is critical for steady state control of alveolar macrophage numbers and the transition of neutrophils from the lung into the airways in OVA-driven allergic asthma. However, C5aR1 activation of LysM-expressing cells plays a surprisingly minor role in the recruitment and activation of such cells and the development of the allergic phenotype in OVA-driven experimental

Inhibition of pan neurotrophin receptor p75 attenuates diesel particulate-induced enhancement of allergic airway responses in C57/B16J mice.

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Farraj, Aimen K; Haykal-Coates, Najwa; Ledbetter, Allen D; Evansky, Paul A; Gavett, Stephen H

2006-06-01

Recent investigations have linked neurotrophins, including nerve growth factor (NGF), neurotrophin-3 (NT-3), and brain-derived neurotrophic factor (BDNF), to allergic airways diseases. Antibody blockade of NGF attenuates airway resistance in allergic mice. Diesel exhaust particle (DEP) exposure has been linked to asthma exacerbation in many cities with vehicular traffic congestion. We tested the hypothesis that DEP-induced enhancement of the hallmark features of allergic airway disease in a murine model is dependent on the function of the pan neurotrophin receptor p75. Ovalbumin (OVA)-sensitized C57B1/6J mice were intranasally instilled with an antibody against the p75 receptor or saline alone 1 h before OVA challenge. The mice were then exposed nose-only to the PM2.5 fraction of SRM2975 DEP or air alone for 5 h beginning 1 h after OVA challenge. Two days later, air-exposed OVA-allergic mice developed a small but insignificant increase in methacholine-induced airflow obstruction relative to air-exposed, vehicle-sensitized mice. DEP-exposed OVA-allergic mice had a significantly greater degree of airway obstruction than all other groups. Instillation of anti-p75 significantly attenuated the DEP-induced increase in airway obstruction in OVA-allergic mice to levels similar to non-sensitized mice. The DEP-induced exacerbation of allergic airway responses may, in part, be mediated by neurotrophins.

Fusion-Expressed CTB Improves Both Systemic and Mucosal T-Cell Responses Elicited by an Intranasal DNA Priming/Intramuscular Recombinant Vaccinia Boosting Regimen

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Sugan Qiu

2014-01-01

Full Text Available Previous study showed that CTB (Cholera toxin subunit B can be used as a genetic adjuvant to enhance the systemic immune responses. To further investigate whether it can also be used as a genetic adjuvant to improve mucosal immune responses, we constructed DNA and recombinant Tiantan vaccinia (rTTV vaccines expressing OVA-CTB fusion antigen. Female C57BL/6 mice were immunized with an intranasal DNA priming/intramuscular rTTV boosting regimen. OVA specific T-cell responses were measured by IFN-γ ELISPOT and specific antibody responses were determined by ELISA. Compared to the nonadjuvant group (pSV-OVA intranasal priming/rTTV-OVA intramuscular boosting, pSV-OVA-CTB intranasal priming/rTTV-OVA-CTB intramuscular boosting group significantly improved the magnitudes of T-cell responses at spleen (1562±567 SFCs/106 splenocytes versus 330±182 SFCs/106 splenocytes, P<0.01, mesenteric LN (96±83 SFCs/106 lymphocytes versus 1±2 SFCs/106 lymphocytes, P<0.05, draining LNs of respiratory tract (109±60 SFCs/106 lymphocytes versus 2±2 SFCs/106 lymphocytes, P<0.01 and female genital tract (89±48 SFCs/106 lymphocytes versus 23±21 SFCs/106 lymphocytes, P<0.01. These results collectively demonstrated that fusion-expressed CTB could act as a potent adjuvant to improve both systemic and mucosal T-cell responses.

Involvement of central nervous system in the schistosomiasis

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Teresa Cristina de Abreu Ferrari

2004-08-01

Full Text Available The involvement of the central nervous system (CNS by schistosomes may or may not determine clinical manifestations. When symptomatic, neuroschistosomiasis (NS is one of the most severe presentations of schistosomal infection. Considering the symptomatic form, cerebral involvement is almost always due to Schistosoma japonicum and the spinal cord disease, caused by S. mansoni or S. haematobium. Available evidence suggests that NS depends basically on the presence of parasite eggs in the nervous tissue and on the host immune response. The patients with cerebral NS usually have the clinical manifestations of increased intracranial pressure associated with focal neurological signs; and those with schistosomal myeloradiculopathy (SMR present rapidly progressing symptoms of myelitis involving the lower cord, usually in association with the involvement of the cauda esquina roots. The diagnosis of cerebral NS is established by biopsy of the nervous tissue and SMR is usually diagnosed according to a clinical criterion. Antischistosomal drugs, corticosteroids and surgery are the resourses available for treating NS. The outcome is variable and is better in cerebral disease.

Immunomodulatory Effects of Galectin-1 on an IgE-Mediated Allergic Conjunctivitis Model

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Mello, Claudia Bosnic; Ramos, Lisandra [UNIFESP; Gimenes, Alexandre Dantas [UNIFESP; Andrade, Teresa Raquel de Moraes [UNIFESP; Oliani, Sonia Maria [UNIFESP; Gil, Cristiane Damas [UNIFESP

2015-01-01

PURPOSE. Galectin (Gal)-1, a lectin found at sites of immune privilege with critical role in the inflammation, has been poorly investigated in the ocular inflammatory diseases. Here, we evaluated the therapeutic potential of Gal-1 in ocular allergy using a model of ovalbumin (OVA)-induced AC.METHODS. OVA-immunized BALB/c male mice were challenged with eye drops containing OVA on days 14 through 16 with a subset of animals pretreated intraperitoneally with recombinant Gal-1 (rGal-1) or dexamet...

Curcumin Ingestion Inhibits Mastocytosis and Suppresses Intestinal Anaphylaxis in a Murine Model of Food Allergy.

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Shannon R M Kinney

Full Text Available IgE antibodies and mast cells play critical roles in the establishment of allergic responses to food antigens. Curcumin, the active ingredient of the curry spice turmeric, has anti-inflammatory properties, and thus may have the capacity to regulate Th2 cells and mucosal mast cell function during allergic responses. We assessed whether curcumin ingestion during oral allergen exposure can modulate the development of food allergy using a murine model of ovalbumin (OVA-induced intestinal anaphylaxis. Herein, we demonstrate that frequent ingestion of curcumin during oral OVA exposure inhibits the development of mastocytosis and intestinal anaphylaxis in OVA-challenged allergic mice. Intragastric (i.g. exposure to OVA in sensitized BALB/c mice induced a robust IgE-mediated response accompanied by enhanced OVA-IgE levels, intestinal mastocytosis, elevated serum mMCP-1, and acute diarrhea. In contrast, mice exposed to oral curcumin throughout the experimental regimen appeared to be normal and did not exhibit intense allergic diarrhea or a significant enhancement of OVA-IgE and intestinal mast cell expansion and activation. Furthermore, allergic diarrhea, mast cell activation and expansion, and Th2 responses were also suppressed in mice exposed to curcumin during the OVA-challenge phase alone, despite the presence of elevated levels of OVA-IgE, suggesting that curcumin may have a direct suppressive effect on intestinal mast cell activation and reverse food allergy symptoms in allergen-sensitized individuals. This was confirmed by observations that curcumin attenuated the expansion of both adoptively transferred bone marrow-derived mast cells (BMMCs, and inhibited their survival and activation during cell culture. Finally, the suppression of intestinal anaphylaxis by curcumin was directly linked with the inhibition of NF-κB activation in curcumin-treated allergic mice, and curcumin inhibited the phosphorylation of the p65 subunit of NF-κB in BMMCs. In

In vivo and ex vivo EPR detection of spin-labelled ovalbumin in mice.

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Abramović, Zrinka; Brgles, Marija; Habjanec, Lidija; Tomasić, Jelka; Sentjurc, Marjeta; Frkanec, Ruza

2010-10-01

In this study, spin-labelled ovalbumin (SL-OVA), free or entrapped in liposomes, was administered to mice subcutaneously (s.c.) or intravenously (i.v.) with the aim to determine the conditions for pharmacokinetic studies of spin-labelled proteins by EPR and to measure the time course of SL-OVA distribution in vivo in live mice and ex vivo in isolated organs. Upon s.c. administration, the decay of the EPR signal was followed for 60min at the site of application using an L-band EPR spectrometer. Within this time period, the signal of free SL-OVA was diminished by about 70%. It was estimated with the help of the oxidizing agent K(3)[(FeCN)(6)] that approximately 30% was a consequence of the spin label reduction to EPR non-visible hydroxylamine and about 40% was due to the SL-OVA elimination from the site of measurement. For liposome encapsulated SL-OVA, the intensity diminished only by approx. 40% in the same period, indicating that liposomes successfully protect the protein from reduction. EPR signal could not be detected directly over live mouse organs within 60min after s.c. application of SL-OVA. With the available L-band EPR spectrometer, the measurements at the site of s.c. application are possible if the amount of SL-OVA applied to a mouse is more than 3mg. For the pharmacokinetic studies of the protein distribution in organs after s.c. or i.v. injection the concentration of the spin-labelled protein should be more than 0.5mmol/kg. After i.v. administration, only ex vivo measurements were possible using an X-band EPR spectrometer, since the total amount of SL-OVA was not sufficient for in vivo detection and also because of rapid reduction of nitroxide. After 2min, the protein was preferentially distributed to liver and, to a smaller extent, to spleen.

Development and characterization of an effective food allergy model in Brown Norway rats.

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Abril-Gil, Mar; Garcia-Just, Alba; Pérez-Cano, Francisco J; Franch, Àngels; Castell, Margarida

2015-01-01

Food allergy (FA) is an adverse health effect produced by the exposure to a given food. Currently, there is no optimal animal model of FA for the screening of immunotherapies or for testing the allergenicity of new foods. The aim of the present study was to develop an effective and rapid model of FA in Brown Norway rats. In order to establish biomarkers of FA in rat, we compared the immune response and the anaphylactic shock obtained in this model with those achieved with only intraperitoneal immunization. Rats received an intraperitoneal injection of ovalbumin (OVA) with alum and toxin from Bordetella pertussis, and 14 days later, OVA by oral route daily for three weeks (FA group). A group of rats receiving only the i.p. injection (IP group) were also tested. Serum anti-OVA IgE, IgG1, IgG2a, IgG2b and IgA antibodies were quantified throughout the study. After an oral challenge, body temperature, intestinal permeability, motor activity, and mast cell protease II (RMCP-II) levels were determined. At the end of the study, anti-OVA intestinal IgA, spleen cytokine production, lymphocyte composition of Peyer's patches and mesenteric lymph nodes, and gene expression in the small intestine were quantified. Serum OVA-specific IgG1, IgG2a and IgG2b concentrations rose with the i.p. immunization but were highly augmented after the oral OVA administration. Anti-OVA IgE increased twofold during the first week of oral OVA gavage. The anaphylaxis in both IP and FA groups decreased body temperature and motor activity, whereas intestinal permeability increased. Interestingly, the FA group showed a much higher RMCP II serum protein and intestinal mRNA expression. These results show both an effective and relatively rapid model of FA assessed by means of specific antibody titres and the high production of RMCP-II and its intestinal gene expression.

Development and characterization of an effective food allergy model in Brown Norway rats.

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Mar Abril-Gil

Full Text Available Food allergy (FA is an adverse health effect produced by the exposure to a given food. Currently, there is no optimal animal model of FA for the screening of immunotherapies or for testing the allergenicity of new foods.The aim of the present study was to develop an effective and rapid model of FA in Brown Norway rats. In order to establish biomarkers of FA in rat, we compared the immune response and the anaphylactic shock obtained in this model with those achieved with only intraperitoneal immunization.Rats received an intraperitoneal injection of ovalbumin (OVA with alum and toxin from Bordetella pertussis, and 14 days later, OVA by oral route daily for three weeks (FA group. A group of rats receiving only the i.p. injection (IP group were also tested. Serum anti-OVA IgE, IgG1, IgG2a, IgG2b and IgA antibodies were quantified throughout the study. After an oral challenge, body temperature, intestinal permeability, motor activity, and mast cell protease II (RMCP-II levels were determined. At the end of the study, anti-OVA intestinal IgA, spleen cytokine production, lymphocyte composition of Peyer's patches and mesenteric lymph nodes, and gene expression in the small intestine were quantified.Serum OVA-specific IgG1, IgG2a and IgG2b concentrations rose with the i.p. immunization but were highly augmented after the oral OVA administration. Anti-OVA IgE increased twofold during the first week of oral OVA gavage. The anaphylaxis in both IP and FA groups decreased body temperature and motor activity, whereas intestinal permeability increased. Interestingly, the FA group showed a much higher RMCP II serum protein and intestinal mRNA expression.These results show both an effective and relatively rapid model of FA assessed by means of specific antibody titres and the high production of RMCP-II and its intestinal gene expression.

Natural CD8+25+ regulatory T cell-secreted exosomes capable of suppressing cytotoxic T lymphocyte-mediated immunity against B16 melanoma

International Nuclear Information System (INIS)

Xie, Yufeng; Zhang, Xueshu; Zhao, Tuo; Li, Wei; Xiang, Jim

2013-01-01

Highlights: •CD8 + 25 + regulatory T cells secrete tolerogenic exosomes. •CD8 + 25 + regulatory T cell-derived exosomes exhibit immunosuppressive effect. •CD8 + 25 + regulatory T cell-derived exosomes inhibit antitumor immunity. -- Abstract: Natural CD4 + 25 + and CD8 + 25 + regulatory T (Tr) cells have been shown to inhibit autoimmune diseases. Immune cells secrete exosomes (EXOs), which are crucial for immune regulation. However, immunomodulatory effect of natural Tr cell-secreted EXOs is unknown. In this study, we purified natural CD8 + 25 + Tr cells from C57BL/6 mouse naive CD8 + T cells, and in vitro amplified them with CD3/CD28 beads. EXOs (EXO Tr ) were purified from Tr cell’s culture supernatants by differential ultracentrifugation and analyzed by electron microscopy, Western blot and flow cytometry. Our data showed that EXO Tr had a “saucer” or round shape with 50–100 nm in diameter, contained EXO-associated markers LAMP-1 and CD9, and expressed natural Tr cell markers CD25 and GITR. To assess immunomodulatory effect, we i.v. immunized C57BL/6 mice with ovalbumin (OVA)-pulsed DCs (DC OVA ) plus Tr cells or EXO Tr , and then assessed OVA-specific CD8 + T cell responses using PE-H-2K b /OVA tetramer and FITC-anti-CD8 antibody staining by flow cytometry and antitumor immunity in immunized mice with challenge of OVA-expressing BL6–10 OVA melanoma cells. We demonstrated that DC OVA -stimulated CD8 + T cell responses and protective antitumor immunity significantly dropped from 2.52% to 1.08% and 1.81% (p OVA (p Tr , respectively. Our results indicate that natural CD8 + 25 + Tr cell-released EXOs, alike CD8 + 25 + Tr cells, can inhibit CD8 + T cell responses and antitumor immunity. Therefore, EXOs derived from natural CD4 + 25 + and CD8 + 25 + Tr cells may become an alternative for immunotherapy of autoimmune diseases

Therapeutic potential of combined anti-IL-1β IgY and anti-TNF-α IgY in guinea pigs with allergic rhinitis induced by ovalbumin.

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Guo-Zhu, Hu; Xi-Ling, Zhu; Zhu, Wen; Li-Hua, Wu; Dan, He; Xiao-Mu, Wu; Wen-Yun, Zhou; Wei-Xu, Hu

2015-03-01

We have previously demonstrated that anti-IL-1β immunoglobulin yolk(IgY) inhibits pathological responses in allergic asthma guinea pigs induced by ovalbumin(OVA). This study aims to determine whether the combined blockade of IL-1β and TNF-α can more effectively inhibit allergic inflammation in allergic rhinitis(AR) guinea pigs induced by OVA. Healthy guinea pigs treated with saline were used as the healthy control. The AR guinea pigs induced by OVA were randomly divided into (1) the AR model group containing negative control animals treated with intranasal saline; (2) the 0.1% non-specific IgY treatment group treated with non-specific IgY; (3) the 0.1% anti-TNF-α IgY treatment group treated with 0.1% anti-TNF-α IgY; (4) the 0.1% anti-IL-1β IgY treatment group treated with 0.1% anti-IL-1β IgY; (5) the 0.1% combined anti-IL-1β IgY and anti-TNF-α IgY treatment group treated with 0.1% combined anti-IL-1β IgY and anti-TNF-α IgY; and (6) the fluticasone propionate treatment group treated with fluticasone propionate. Cytokines were measured using an enzyme-linked immunosorbent assay. The results showed that IL-1β, IL-5, IL-9, IL-13, IL-18, IL-22, IL-33, TNF-α, TGF-β1 and OVA-specific IgE levels in the peripheral blood (PB) and nasal lavage fluid (NLF) significantly decreased at 2h, 4h or 8h in the 0.1% combined anti-IL-1β IgY and anti-TNF-α IgY treatment group compared to the AR model group and the 0.1% non-specific IgY treatment group (P<0.05). The data suggest that blockade of IL-1β and TNF-α by intranasal instillation of combined anti-IL-1β IgY and anti-TNF-α IgY could be a potential alternative strategy for preventing and treating allergic rhinitis. Copyright © 2014. Published by Elsevier B.V.

Epicutaneous immunotherapy on intact skin using a new delivery system in a murine model of allergy.

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Mondoulet, L; Dioszeghy, V; Ligouis, M; Dhelft, V; Dupont, C; Benhamou, P-H

2010-04-01

Allergen-specific immunotherapy, subcutaneous immunotherapy (SCIT) or oral, has been used for almost a century to redirect inappropriate immune responses in atopic patients. A new mode of administration through the intact skin [epicutaneous immunotherapy (EPIT)], using an original epicutaneous delivery system, may represent an alternative to these classical methods. Proof of concept of efficacy of EPIT on intact skin in mice sensitized to aeroallergens or food allergens. Mice were sensitized to pollen (n=18), house dust mite (HDM, n=24), ovalbumin (OVA, n=18) or peanut (n=18), and allocated to four groups: EPIT, SCIT, not treated (NT) and control. Specific Ig (sIg)E, sIgG1 and sIgG2a were monitored. After 8 weeks of treatment, plethysmography was performed after aerosol provocation with appropriate allergens. At the highest doses of methacholine, pause enhancement (Penh) values were significantly decreased in the EPIT group vs. the sensitized NT groups (7.5 vs. 12.3 - pollen, 7.6 vs. 8.9 - HDM, 11.5 vs. 14.5 - OVA, 7.6 vs. 12.8 - peanut, respectively) (P<0.05). With all the allergens tested, Penh values were similar in SCIT, EPIT and control. IgG2a for pollen, HDM, OVA and peanuts were significantly increased in the EPIT group vs. NT: 0.97 vs. 0.42 microg/mL, 2.5 vs. 0.46 microg/mL, 0.39 vs. 0.05 microg/mL and 15.0 vs. 5.5 microg/mL, respectively (P<0.05). There were no significant differences between EPIT and SCIT groups. The IgE/IgG2a ratio decreased significantly in the EPIT group for the four allergens from 70 to 58 (pollen), 175 to 26 (HDM), 5433 to 120 (OVA) and 49 to 6 (peanut), respectively (P<0.05). In mice sensitized to the four allergens tested, EPIT was as efficacious as SCIT, considered as the reference immunotherapy. These first results have to be confirmed by clinical studies.

In silico analysis of the fucosylation-associated genome of the human blood fluke Schistosoma mansoni: cloning and characterization of the fucosyltransferase multigene family.

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Peterson, Nathan A; Anderson, Tavis K; Yoshino, Timothy P

2013-01-01

Fucosylated glycans of the parasitic flatworm Schistosoma mansoni play key roles in its development and immunobiology. In the present study we used a genome-wide homology-based bioinformatics approach to search for genes that contribute to fucosylated glycan expression in S. mansoni, specifically the α2-, α3-, and α6-fucosyltransferases (FucTs), which transfer L-fucose from a GDP-L-fucose donor to an oligosaccharide acceptor. We identified and in silico characterized several novel schistosome FucT homologs, including six α3-FucTs and six α6-FucTs, as well as two protein O-FucTs that catalyze the unrelated transfer of L-fucose to serine and threonine residues of epidermal growth factor- and thrombospondin-type repeats. No α2-FucTs were observed. Primary sequence analyses identified key conserved FucT motifs as well as characteristic transmembrane domains, consistent with their putative roles as fucosyltransferases. Most genes exhibit alternative splicing, with multiple transcript variants generated. A phylogenetic analysis demonstrated that schistosome α3- and α6-FucTs form monophyletic clades within their respective gene families, suggesting multiple gene duplications following the separation of the schistosome lineage from the main evolutionary tree. Quantitative decreases in steady-state transcript levels of some FucTs during early larval development suggest a possible mechanism for differential expression of fucosylated glycans in schistosomes. This study systematically identifies the complete repertoire of FucT homologs in S. mansoni and provides fundamental information regarding their genomic organization, genetic variation, developmental expression, and evolutionary history.

A Novel Therapeutic Vaccine for Metastatic Mammary Carcinoma: Focusing MHC/Peptide Complexes to Lipid Rafts

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2006-11-01

reportable outcomes). Briefly, the T cell lymphoma EL4 and the immortalized fibroblast cell line DAP (both expressing ova) were used to measure...and Use Committee. Cells , transfections, and antibodies B16.BL6 8.2, A20, EL4 and EL4 /ova were cultured as described (20-22). NIH3T3 cells were...types can donate MHC class I molecules to DC. To determine if the levels of MHC class I on the donor cell affected the efficiency of transfer, EL4 /ova

In vivo fertilizing capacity of deep frozen boar semen packaged in plastic bags and maxi-straws.

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Bwanga, C O; Hofmo, P O; Grevle, I S; Einarsson, S; Rodriguez-Martinez

1991-05-01

Pooled ejaculates from six fertile boars were frozen under controlled conditions in Teflon FEP-film plastic bags (5 ml) and maxi-straws (2.5 ml) using 3% glycerol as cryoprotectant. The percentages of both post-thaw motility and normal apical ridges were significantly higher (P less than 0.001) for the bags (54.5 and 75%) than for the maxi-straws (40.1 and 59.4%) respectively. For evaluation of the in vivo fertilizing capacity of the frozen-thawed spermatozoa, 26 gilts were inseminated once 24 h after the first observation of standing reflex in their second oestrus, with 5 ml of semen (containing 5 billion spermatozoa) reconstituted in 80 ml of BTS from either bags or maxi-straws. Ova were recovered from the oviducts/uteri 2-4 days following insemination and examined for cleavage and sperm binding to the zona pellucida (ZP). Significantly higher rates (P less than 0.02) of fertilized ova were found in the bag-inseminated (75%) than in maxi-straw inseminated gilts (63%); and similarly their ova had significantly more spermatozoa in the ZP, irrespective of whether they were fertilized or nonfertilized. This study confirmed that the plastic bags are suitable and may be used for packaging single insemination doses of deep frozen boar semen for routine A.I. work.

Unconditional government cash transfers in support of orphaned and vulnerable adolescents in western Kenya: Is there an association with psychological wellbeing?

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Sylvia Shangani

Full Text Available Orphaned and vulnerable adolescents (OVA in sub-Saharan Africa are at greater risk for adverse psychological outcomes compared with their non-OVA counterparts. Social interventions that provide cash transfers (CTs have been shown to improve health outcomes among young people, but little is known about their impact on the psychological wellbeing of OVA.Among OVA in western Kenya, we assessed the association between living in a household that received monthly unconditional government CTs and psychological wellbeing.We examined the likelihood of depression, anxiety, post-traumatic stress symptoms (PTSS and positive future outlook among 655 OVA aged between 10 and 18 years who lived in 300 randomly selected households in western Kenya that either received or did not receive unconditional monthly CTs.The mean age was 14.0 (SD 2.4 years and 329 (50.2% of the participants were female while 190 (29.0% were double orphans whose biological parents were both deceased. After adjusting for socio-demographic, caregiver, and household characteristics and accounting for potential effects of participant clustering by sub-location of residence, OVA living in CT households were more likely to have a positive future outlook (odds ratio [OR] 1.47, 95% confidence interval [CI] 1.08, 1.99, less likely to be anxious (OR 0.57, 95% CI 0.42, 0.78, and less likely to have symptoms of post-traumatic stress (OR 0.50, 95% CI 0.29, 0.89. We did not find statistically significant differences in odds of depression by CT group.OVA in CT households reported better psychological wellbeing compared to those in households not receiving CTs. CT interventions may be effective for improving psychological wellbeing among vulnerable adolescents in socioeconomically deprived households.

Recombinant Mycobacterium bovis BCG producing IL-18 reduces IL-5 production and bronchoalveolar eosinophilia induced by an allergic reaction.

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Biet, F; Duez, C; Kremer, L; Marquillies, P; Amniai, L; Tonnel, A-B; Locht, C; Pestel, J

2005-08-01

Allergic reactions occur through the exacerbated induction of a Th2 cell type expression profile and can be prevented by agents favoring a Th1 profile. Bacillus Calmette-Guérin (BCG) is able to induce high IFN-gamma levels and has been shown to decrease experimentally induced allergy. The induction of IFN-gamma is mediated by interleukin (IL)-12 known to be secreted upon mycobacterial infections and can be enhanced by IL-18 acting in synergy with IL-12. We evaluated the ability of a recombinant BCG strain producing IL-18 (rBCG) to modify the Th2 type responses in a murine model of ovalbumin (OVA)-dependent allergic reaction. Mice were injected intraperitoneally or intranasally with OVA at days 0 and 15 and exposed to an OVA aerosol challenge at days 29, 30, 31 and 34. At days 0 and 15, two additional groups of mice received OVA together with 5 x 10(6) colony forming units of either rBCG or nonrecombinant BCG. A time-course analysis of OVA-specific immunoglobulin (Ig)E, IgG1 and IgG2a levels indicated no significant difference between the three groups of mice. However, following in vitro stimulation with OVA, lymph node cells from rBCG-treated mice produced less IL-5 and more IFN-gamma than those of mice injected with nonrecombinant BCG. In addition, 48 h after the last OVA challenge, a strong reduction of bronchoalveolar eosinophilia was found in the rBCG-injected mice compared to the nontreated or nonrecombinant BCG-treated groups. These results indicate that the production of IL-18 by rBCG may enhance the immunomodulatory properties of BCG that suppress pulmonary Th2 responses and, in particular, decrease airway eosinophilia.

Anti-inflammatory effects of Tat-Annexin protein on ovalbumin-induced airway inflammation in a mouse model of asthma

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Lee, Sun Hwa; Kim, Dae Won; Kim, Hye Ri; Woo, Su Jung; Kim, So Mi; Jo, Hyo Sang [Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702 (Korea, Republic of); Jeon, Seong Gyu [Department of Life Science, Pohang University of Science and Technology, Pohang 790-784 (Korea, Republic of); Cho, Sung-Woo [Department of Biochemistry and Molecular Biology, University of Ulsan, College of Medicine, Seoul 138-736 (Korea, Republic of); Park, Jong Hoon [Department of Biological Science, Sookmyung Women' s University, Seoul 140-742 (Korea, Republic of); Won, Moo Ho [Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon 200-701 (Korea, Republic of); Park, Jinseu [Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702 (Korea, Republic of); Eum, Won Sik, E-mail: wseum@hallym.ac.kr [Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702 (Korea, Republic of); Choi, Soo Young, E-mail: sychoi@hallym.ac.kr [Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702 (Korea, Republic of)

2012-01-20

Highlights: Black-Right-Pointing-Pointer We construct a cell permeable Tat-ANX1 fusion protein. Black-Right-Pointing-Pointer We examined the protective effects of Tat-ANX1 protein on OVA-induced asthma in animal models. Black-Right-Pointing-Pointer Transduced Tat-ANX1 protein protects from the OVA-induced production of cytokines and eosinophils in BAL fluid. Black-Right-Pointing-Pointer Tat-ANX1 protein markedly reduced OVA-induced MAPK in lung tissues. Black-Right-Pointing-Pointer Tat-ANX1 protein could be useful as a therapeutic agent for lung disorders including asthma. -- Abstract: Chronic airway inflammation is a key feature of bronchial asthma. Annexin-1 (ANX1) is an anti-inflammatory protein that is an important modulator and plays a key role in inflammation. Although the precise action of ANX1 remains unclear, it has emerged as a potential drug target for inflammatory diseases such as asthma. To examine the protective effects of ANX1 protein on ovalbumin (OVA)-induced asthma in animal models, we used a cell-permeable Tat-ANX1 protein. Mice sensitized and challenged with OVA antigen had an increased amount of cytokines and eosinophils in their bronchoalveolar lavage (BAL) fluid. However, administration of Tat-ANX1 protein before OVA challenge significantly decreased the levels of cytokines (interleukin (IL)-4, IL-5, and IL-13) and BAL fluid in lung tissues. Furthermore, OVA significantly increased the activation of mitogen-activated protein kinase (MAPK) in lung tissues, whereas Tat-ANX1 protein markedly reduced phosphorylation of MAPKs such as extracellular signal-regulated protein kinase, p38, and stress-activated protein kinase/c-Jun N-terminal kinase. These results suggest that transduced Tat-ANX1 protein may be a potential protein therapeutic agent for the treatment of lung disorders including asthma.

The student and the ovum: The lack of autonomy and informed consent in trading genes for tuition

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Papadimos Alexa T

2004-07-01

Full Text Available Abstract Rising tuition costs have forced university students to become creative in finding ways to fund their education. Some female university students have decided that ova donation may be an acceptable alternative in which to pay for their tuition. This alternative presents itself because of the insufficient number of ova available for assisted reproduction and emerging stem cell technologies. Young female university students are encouraged by Internet sources and respectable electronic and print media to donate their ova in the cause of assisted reproduction for monetary compensation. While university students generally exhibit autonomy, the constraining influence of their financial predicament compromises the elements of informed consent (voluntariness, competence, capacity, understanding, and disclosure as to their making an autonomous decision in regard to egg donation. Thus, any moral possibility of giving informed consent is negated. Informed consent can only occur through autonomy. A female university student in need of financial resources to pay for her education cannot make an autonomous choice to trade her genes for tuition. Donated ova are not only needed for assisted reproduction, but for stem cell technologies. While the long-term health of women who donate their ova is of concern (a potential risk of cancer after long term use of ovulation induction, of equal concern is the possibility of a growth in the trade of ova targeting third world and Eastern European women where the precedence for autonomy and informed consent is not well established.

Curdlan sulfate-O-linked quaternized chitosan nanoparticles: potential adjuvants to improve the immunogenicity of exogenous antigens via intranasal vaccination.

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Zhang, Shu; Huang, Shengshi; Lu, Lu; Song, Xinlei; Li, Pingli; Wang, Fengshan

2018-01-01

The development of ideal vaccine adjuvants for intranasal vaccination can provide convenience for many vaccinations. As an ideal intranasal vaccine adjuvant, it should have the properties of assisting soluble antigens to pass the mucosal barrier and potentiating both systemic and mucosal immunity via nasal administration. By using the advantages of polysaccharides, which can promote both T-helper 1 and 2 responses, curdlan sulfate (CS)- O -(2-hydroxyl)propyl-3-trimethyl ammonium chitosan chloride ( O -HTCC) nanoparticles were prepared by interacting CS with O -HTCC, and the adjuvancy of the nanoparticles was investigated. The results showed that the polysaccharide-based nanoparticles induced the proliferation and activation of antigen-presenting cells. High protein-loading efficiency was obtained by testing with the model antigen ovalbumin (Ova), and the Ova adsorbed onto the cationic CS/ O -HTCC complexes was taken up easily by the epithelium. To evaluate the capacity of the Ova/CS/ O -HTCC nanoparticles for immune enhancement in vivo, we collected and analyzed immunocytes, serum, and mucosal lavage fluid from intranasally vaccinated mice. The results showed that Ova/CS/ O -HTCC nanoparticles induced activation and maturation of antigen-presenting cells and provoked the proliferation and differentiation of lymphocytes more significantly compared to the immunization of Ova mixed with aluminum hydroxide gel. Furthermore, CS/ O -HTCC evoked a significantly higher level of Ova-specific antibodies. Therefore, these results suggest that CS/ O -HTCC nanoparticles are ideal vaccine adjuvants for soluble antigens used in intranasal or mucosal vaccination.

Enhancement of antigen-induced eosinophilic inflammation in the airways of mast-cell deficient mice by diesel exhaust particles

International Nuclear Information System (INIS)

Ichinose, Takamichi; Takano, Hirohisa; Miyabara, Yuichi; Sadakaneo, Kaori; Sagai, Masaru; Shibamoto, Takayuki

2002-01-01

The present study was conducted to clarify the involvement of mast cells in the exacerbating effect of diesel exhaust particles (DEP) toward allergic airway inflammation and airway hyperresponsiveness (AHR). Airway inflammation by the infiltration of cosinophils with goblet cell proliferation and AHR, as well as by the production of antigen-specific IgG1 and IgE, in plasma were examined using mast cell-deficient mice (W/W v ) and normal mice (W/W + ). Both groups of mice received ovalbumin (OVA) or OVA+DEP intratracheally. The eosinophilic airway inflammation and goblet cell proliferation promoted by OVA were significantly greater in W/W + than in W/W v . A similar result was observed in AHR, but was not significant among both groups of mice. DEP enhanced OVA induced-allergic airway inflammation, goblet cell proliferation, and development of AHR in W/W v , but not in W/W + . DEP decreased production of antigen-specific IgG1 and IgE in both groups of mice. Mast cells were observed in the submucosal layer of the main bronchus in W/W v . The number of mast cells was significantly decreased by OVA treatment. The results indicate that mast cells are not necessary to enhance airway damage and development of AHR in W/W v by DEP. However, mast cells may be required for the OVA-induced cosinophilic inflammation, airway damage with goblet cell proliferation, and AHR in W/W +

Irradiated mice lose the capacity to 'process' fed antigen for systemic tolerance of delayed-type hypersensitivity

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Bruce, M G; Strobel, S; Hanson, D G; Ferguson, A

1987-12-01

'Intestinal antigen processing' is a function of the gastro-intestinal tract whereby shortly after an animal has been fed an immunogenic protein antigen, such as ovabumin (OVA), a tolerogenic form of the protein is generated and can be detected in the circulation. The effect of damage to the intestinal epithelium on the processing of OVA has been examined in lethally irradiated mice. Irradiated animals were fed 25 mg OVA and their serum collected 1 h later. When this serum was transferred intraperitoneally into naive recipient mice, this did not induce the typical suppression of systemic delayed-type hypersensitivity. Results were similar when the serum donors were at 2 days after irradiation, with crypt hypoplasia, and at 5 days after irradiation when there was reactive crypt hyperplasia. However reconstitution of donors with normal spleen cells immediately after irradiation restored their capacity to generate a tolerogenic form of the antigen. Immunoreactive OVA was detected by ELISA in both tolerizing and non-tolerizing sera, and the immunological properties of these sera were not related to serum levels of OVA after feeding. The results suggest that lymphoid cells may be involved in the phenomenon of antigen processing.

The WHO Collaborating Centre for Research and Control of Schistosomiasis at Niamey, Niger

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Chippaux J-P

1997-01-01

Full Text Available The Centre de Recherche sur les Méningites et les Schistosomes (CERMES is a research institute depending on the Organisation de Coordination et de Coopération pour la lutte contre les Grandes Endémies - a West African Organization for Public Health - devoted to the studies on schistosomiasis and meningitis. The staff includes 32 persons with 11 scientists and one financial officer. The activities of the CERMES involving schistosomiasis concern three research units: (a ecology of human and animal schistosomiasis transmission; the CERMES defined the different patterns of schistosomiasis transmission in Niger (involving African dry savana; in this field, we have shown, (i the existence of important variability in conditions of transmission of S. haematobium and, (ii natural hybridization between parasitic species of the ruminants (S. bovis and S. curassoni and genetic interaction between human and animal parasites; (b definition of morbidity indicators usable for rapid assessment methods, for appraisal of the severity of the disease and for the evaluation of the efficiency of control methods; we have established the correlation between ultrasonographic data and some cheap and simple field indicators; (c immune response and protective immunity induced by recombinant glutathion S-transferase (Sm28, Sb28 and Sh28 in homologous and heterologous animal models including goats, sheep and non human primates (Erythrocebus patas. In Niger, we participate in all control programs against schistosomiasis to define control strategies, to supervise operations and to participate in their evaluation with external experts. International collaborations constitute a frame including four laboratories in Africa and six laboratories in developed countries (Europe and USA

Correlative and dynamic imaging of the hatching biology of Schistosoma japonicum from eggs prepared by high pressure freezing.

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Malcolm K Jones

Full Text Available BACKGROUND: Schistosome eggs must traverse tissues of the intestine or bladder to escape the human host and further the life cycle. Escape from host tissues is facilitated by secretion of immuno-reactive molecules by eggs and the formation of an intense strong granulomatous response by the host which acts to exclude the egg into gut or bladder lumens. Schistosome eggs hatch on contact with freshwater, but the mechanisms of activation and hatching are poorly understood. In view of the lack of knowledge of the behaviour of egg hatching in schistosomes, we undertook a detailed dynamic and correlative study of the hatching biology of Schistosoma japonicum. METHODOLOGY/PRINCIPAL FINDINGS: Hatching eggs of S. japonicum were studied using correlative light and electron microscopy (EM. The hatching behaviour was recorded by video microscopy. EM preparative methods incorporating high pressure freezing and cryo-substitution were used to investigate ultrastructural features of the miracidium and extra-embryonic envelopes in pre-activated and activated eggs, and immediately after eggshell rupture. Lectin cytochemistry was performed on egg tissues to investigate subcellular location of specific carbohydrate groups. CONCLUSIONS/SIGNIFICANCE: The hatching of S. japonicum eggs is a striking phenomenon, whereby the larva is liberated explosively while still encapsulated within its sub-shell envelopes. The major alterations that occur in the egg during activation are scission of the outer envelope-eggshell boundary, autolysis of the cellular inner envelope, and likely hydration of abundant complex and simple polysaccharides in the lacunal space between the miracidial larva and surrounding envelopes. These observations on hatching provide insight into the dynamic activity of the eggs and the biology of schistosomes within the host.

Immunity to Schistosoma mansoni in guinea-pigs vaccinated with radiation-attenuated cercariae. T-cell activation of macrophages for larval killing

International Nuclear Information System (INIS)

Gordon, J.R.; McLaren, D.J.

1988-01-01

This study addresses macrophage activation in guinea-pigs vaccinated with radiation-attenuated cercariae of Schistosom mansoni. Peritoneal exudate macrophages elicited in vaccinated animals by mineral oil injection were activated to kill larval schistosomes in vitro. Killing efficiency is dependent upon the cell:target ratio employed and is enhanced by, but is not strictly dependent on, the presence of specific antibodies. Macrophages co-cultured with parasites release superoxide radicals and hydrogen peroxide, but the use of inhibitors has shown that neither of these reactive oxygen intermediates are the causal agents of cellular cytotoxicity in this system. Oil-elicited macrophages from naive guinea-pigs do not show comparable activation; they can, however, be activated in vitro by incubation with culture supernatant fluids from schistosome antigen-stimulated spleen, or lymph node cells harvested from vaccinated guinea-pigs. Naive macrophages activated in this way kill schistosomula in vitro and release the activation markers IL-l and superoxide anion. The macrophage-activating factor (MAF) present in spleen cell culture supernatant fluids has a MW of 35,000-55,000, but does not have the chemical characteristics of gamma-interferon. (author)

Effects of Sohamhyoong-Tang on Ovalbumin-Induced Allergic Reaction in BALB/c Mice

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So Hyun Jo

2016-01-01

Full Text Available IgE-mediated mast cell degranulation and excessive Th2 cells activation are major features of various allergic diseases. Sohamhyoong-tang has been reported to have anti-inflammatory and antibacterial effects. In this study, we investigated the inhibitory effect of Sohamhyoong-tang extract (SHHTE on allergic symptoms and inflammatory responses in ovalbumin- (OVA- sensitized BALB/c mice. The mice were sensitized with OVA and alum at 2-week intervals and then orally given SHHTE for 13 days followed by intradermal OVA injection. Administration of SHHTE significantly reduced edema formation and inflammatory-cell infiltration in ear tissues. Total and OVA-specific IgEs as well as proinflammatory cytokine TNF-α and Th2-associated cytokine IL-4 levels were lower in the SHHTE-treated group than in the vehicle. SHHTE treatment significantly suppressed both mRNA and protein levels of IL-4 and IL-5 in OVA-stimulated splenocytes. SHHTE decreased Th1 (IFN-γ and Th17 (IL-17a cytokine mRNA expression but increased Treg cytokines (IL-10 and TGF-β1. Moreover, SHHTE significantly inhibited degranulation of RBL-2H3 cell line in a dose-dependent manner. Thus, SHHTE efficiently inhibited the allergic symptoms in an OVA-sensitized mouse model and its action may correlate with the suppression of IgE production by increasing IL-10 and TGF-β1, which can limit the function of other T helper cells and prevent the release of inflammatory mediators from mast cells. These results suggest that SHHTE could be a therapeutic agent for treating various allergic diseases.

A magnetic particles-based chemiluminescence enzyme immunoassay for rapid detection of ovalbumin.

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Feng, Xiao-Li; Ren, Hong-Lin; Li, Yan-Song; Hu, Pan; Zhou, Yu; Liu, Zeng-Shan; Yan, Dong-Ming; Hui, Qi; Liu, Dong; Lin, Chao; Liu, Nan-Nan; Liu, Yan-Yan; Lu, Shi-Ying

2014-08-15

Egg allergy is an important public health and safety concern, so quantification and administration of food or vaccines containing ovalbumin (OVA) are urgently needed. This study aimed to establish a rapid and sensitive magnetic particles-chemiluminescence enzyme immunoassay (MPs-CLEIA) for the determination of OVA. The proposed method was developed on the basis of a double antibodies sandwich immunoreaction and luminol-H2O2 chemiluminescence system. The MPs served as both the solid phase and separator, the anti-OVA MPs-coated polyclonal antibodies (pAbs) were used as capturing antibody, and the horseradish peroxidase (HRP)-labeled monoclonal antibody (mAb) was taken as detecting antibody. The parameters of the method were evaluated and optimized. The established MPs-CLEIA method had a linear range from 0.31 to 100ng/ml with a detection limit of 0.24ng/ml. The assays showed low reactivities and less than 5% of intraassay and interassay coefficients of variation (CVs), and the average recoveries were between 92 and 97%. Furthermore, the developed method was applied in real samples analysis successfully, and the correlation coefficient with the commercially available OVA kit was 0.9976. Moreover, it was more rapid and sensitive compared with the other methods for testing OVA. Copyright © 2014 Elsevier Inc. All rights reserved.

Estrogen and progesterone decrease let-7f microRNA expression and increase IL-23/IL-23 receptor signaling and IL-17A production in patients with severe asthma.

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Newcomb, Dawn C; Cephus, Jacqueline Yvonne; Boswell, Madison G; Fahrenholz, John M; Langley, Emily W; Feldman, Amy S; Zhou, Weisong; Dulek, Daniel E; Goleniewska, Kasia; Woodward, Kimberly B; Sevin, Carla M; Hamilton, Robert G; Kolls, Jay K; Peebles, R Stokes

2015-10-01

Women have an increased prevalence of severe asthma compared with men. IL-17A is associated with severe asthma and requires IL-23 receptor (IL-23R) signaling, which is negatively regulated by let-7f microRNA. We sought to Determine the mechanism by which 17β-estradiol (E2) and progesterone (P4) increase IL-17A production. IL-17A production was determined by using flow cytometry in TH17 cells from women (n = 14) and men (n = 15) with severe asthma. Cytokine levels were measured by using ELISA, and IL-23R and let-7f expression was measured by using quantitative PCR in TH17-differentiated cells from healthy women (n = 13) and men (n = 14). In sham-operated or ovariectomized female mice, 17β-E2, P4, 17β-E2+P4, or vehicle pellets were administered for 3 weeks before ex vivo TH17 cell differentiation. Airway neutrophil infiltration and CXCL1 (KC) expression were also determined in ovalbumin (OVA)-challenged wild-type female recipient mice with an adoptive transfer of OVA-specific TH17 cells from female and male mice. In patients with severe asthma and healthy control subjects, IL-17A production was increased in TH17 cells from women compared with men. IL-23R expression was increased and let-7f expression was decreased in TH17-differentiated cells from women compared with men. In ovariectomized mice IL-17A and IL-23R expression was increased and Let-7f expression was decreased in TH17 cells from mice administered 17β-E2+P4 compared with those administered vehicle. Furthermore, transfer of female OVA-specific TH17 cells increased acute neutrophil infiltration in the lungs of OVA-challenged recipient mice compared with transfer of male OVA-specific TH17 cells. 17β-E2+P4 increased IL-17A production from TH17 cells, providing a potential mechanism for the increased prevalence of severe asthma in women compared with men. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Dietary, nondigestible oligosaccharides and Bifidobacterium breve M-16V suppress allergic inflammation in intestine via targeting dendritic cell maturation.

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de Kivit, Sander; Kostadinova, Atanaska I; Kerperien, JoAnn; Morgan, Mary E; Muruzabal, Veronica Ayechu; Hofman, Gerard A; Knippels, Leon M J; Kraneveld, Aletta D; Garssen, Johan; Willemsen, Linette E M

2017-07-01

Dietary intervention with short-chain galacto-oligosaccharides (scGOS), long-chain fructo-oligosaccharides (lcFOS) and Bifidobacterium breve M-16V ( Bb ) (GF/ Bb ) suppresses food allergic symptoms in mice, potentially via intestinal epithelial cell (IEC)-derived galectin-9. Furthermore, in vitro studies showed galacto- and fructo-oligosaccharides (GF) to enhance the immunomodulatory capacity of a TLR9 ligand representing bacterial CpG DNA when exposed to IEC. In this study, we investigated whether GF/ Bb modulates dendritic cells (DCs) and subsequent Th2 and regulatory T cell (T reg ) frequency in the small intestinal lamina propria (SI-LP). BALB/c mice were fed GF/ Bb during oral OVA sensitization. DC and T cell phenotype were determined in SI-LP mononuclear cells using flow cytometry. Murine bone marrow-derived DCs (BMDCs) were exposed to recombinant galectin-9 or human monocyte-derived DCs (moDCs) and were cultured in IEC-conditioned medium from GF and TLR9 ligand-exposed HT-29 cells. GF/ Bb reduced allergic symptoms and enhanced serum galectin-9 levels, while suppressing activation, restoring phagocytic capacity, and normalizing CD103 expression of SI-LP DCs of OVA-allergic mice. In vitro, galectin-9 suppressed LPS-induced activation markers and cytokine secretion by BMDCs, and IEC-conditioned medium suppressed moDC activation in a galectin-9-dependent manner. Besides suppression of SI-LP DC activation, dietary GF/ Bb also lowered the frequency of activated Th2 cells, while enhancing T reg in the SI-LP of OVA-allergic mice compared to the control diet. Dietary intervention with GF/ Bb enhances galectin-9 and suppresses allergic symptoms of OVA-allergic mice in association with reduced intestinal DC and Th2 activation and increased T reg frequency in these mice. © Society for Leukocyte Biology.

Augmentation of arginase 1 expression by exposure to air pollution exacerbates the airways hyperresponsiveness in murine models of asthma

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Amatullah Hajera

2011-02-01

Full Text Available Abstract Background Arginase overexpression contributes to airways hyperresponsiveness (AHR in asthma. Arginase expression is further augmented in cigarette smoking asthmatics, suggesting that it may be upregulated by environmental pollution. Thus, we hypothesize that arginase contributes to the exacerbation of respiratory symptoms following exposure to air pollution, and that pharmacologic inhibition of arginase would abrogate the pollution-induced AHR. Methods To investigate the role of arginase in the air pollution-induced exacerbation of airways responsiveness, we employed two murine models of allergic airways inflammation. Mice were sensitized to ovalbumin (OVA and challenged with nebulized PBS (OVA/PBS or OVA (OVA/OVA for three consecutive days (sub-acute model or 12 weeks (chronic model, which exhibit inflammatory cell influx and remodeling/AHR, respectively. Twenty-four hours after the final challenge, mice were exposed to concentrated ambient fine particles plus ozone (CAP+O3, or HEPA-filtered air (FA, for 4 hours. After the CAP+O3 exposures, mice underwent tracheal cannulation and were treated with an aerosolized arginase inhibitor (S-boronoethyl-L-cysteine; BEC or vehicle, immediately before determination of respiratory function and methacholine-responsiveness using the flexiVent®. Lungs were then collected for comparison of arginase activity, protein expression, and immunohistochemical localization. Results Compared to FA, arginase activity was significantly augmented in the lungs of CAP+O3-exposed OVA/OVA mice in both the sub-acute and chronic models. Western blotting and immunohistochemical staining revealed that the increased activity was due to arginase 1 expression in the area surrounding the airways in both models. Arginase inhibition significantly reduced the CAP+O3-induced increase in AHR in both models. Conclusions This study demonstrates that arginase is upregulated following environmental exposures in murine models of

Elm Tree (Ulmus parvifolia) Bark Bioprocessed with Mycelia of Shiitake (Lentinus edodes) Mushrooms in Liquid Culture: Composition and Mechanism of Protection against Allergic Asthma in Mice.

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Kim, Sung Phil; Lee, Sang Jong; Nam, Seok Hyun; Friedman, Mendel

2016-02-03

Mushrooms can break down complex plant materials into smaller, more digestible and bioactive compounds. The present study investigated the antiasthma effect of an Ulmus parvifolia bark extract bioprocessed in Lentinus edodes liquid mycelium culture (BPUBE) against allergic asthma in chicken egg ovalbumin (OVA)-sensitized/challenged mice. BPUBE suppressed total IgE release from U266B1 cells in a dose-dependent manner without cytotoxicity. Inhibitory activity of BPUBE against OVA-specific IgE secretion in bronchoalveolar lavage fluid (BALF) was observed in OVA-sensitized/challenged asthmatic mice. BPUBE also inhibited OVA-specific IgG and IgG1 secretion into serum from the allergic mice, suggesting the restoration of a Th2-biased immune reaction to a Th1/Th2-balanced status, as indicated by the Th1/Th2 as well as regulatory T cell (Treg) cytokine profile changes caused by BPUBE in serum or BALF. Inflammatory cell counts in BALF and lung histology showed that leukocytosis and eosinophilia induced by OVA-sensitization/challenge were inhibited by the oral administration of BPUBE. Amelioration of eosinophil infiltration near the trachea was associated with reduced eotaxin and vascular cell adhesion molecule-1 (VCAM-1) levels. Changes in proinflammatory mediator levels in BALF suggest that BPUBE decreased OVA-sensitization-induced elevation of leukotriene C4 (LTC4) and prostaglandin D2 (PGD2). The finding that asthma-associated biomarker levels of OVA-sensitized/challenged mice were much more inhibited with BPUBE treatment than NPUBE (not-bioprocessed Ulmus parvifolia extract) treatment suggested the production of new bioactive compounds by the mushroom mycelia that may be involved in enhancing the observed antiasthmatic properties. The possible relation of the composition determined by proximate analysis and GC/MS to observed bioactivity is discussed. The results suggest that the elm tree (Ulmus parvifolia) bark bioprocessed with mycelia of shiitake (Lentinus edodes

Adsorption, aggregation, and desorption of proteins on smectite particles.

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Kolman, Krzysztof; Makowski, Marcin M; Golriz, Ali A; Kappl, Michael; Pigłowski, Jacek; Butt, Hans-Jürgen; Kiersnowski, Adam

2014-10-07

We report on adsorption of lysozyme (LYS), ovalbumin (OVA), or ovotransferrin (OVT) on particles of a synthetic smectite (synthetic layered aluminosilicate). In our approach we used atomic force microscopy (AFM) and quartz crystal microbalance (QCM) to study the protein-smectite systems in water solutions at pH ranging from 4 to 9. The AFM provided insights into the adhesion forces of protein molecules to the smectite particles, while the QCM measurements yielded information about the amounts of the adsorbed proteins, changes in their structure, and conditions of desorption. The binding of the proteins to the smectite surface was driven mainly by electrostatic interactions, and hence properties of the adsorbed layers were controlled by pH. At high pH values a change in orientation of the adsorbed LYS molecules and a collapse or desorption of OVA layer were observed. Lowering pH to the value ≤ 4 caused LYS to desorb and swelling the adsorbed OVA. The stability of OVT-smectite complexes was found the lowest. OVT revealed a tendency to desorb from the smectite surface at all investigated pH. The minimum desorption rate was observed at pH close to the isoelectric point of the protein, which suggests that nonspecific interactions between OVT and smectite particles significantly contribute to the stability of these complexes.

Antigen Requirements for Efficient Priming of CD8+ T Cells by Leishmania major-Infected Dendritic Cells

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Bertholet, Sylvie; Debrabant, Alain; Afrin, Farhat; Caler, Elisabeth; Mendez, Susana; Tabbara, Khaled S.; Belkaid, Yasmine; Sacks, David L.

2005-01-01

CD4+ and CD8+ T-cell responses have been shown to be critical for the development and maintenance of acquired resistance to infections with the protozoan parasite Leishmania major. Monitoring the development of immunodominant or clonally restricted T-cell subsets in response to infection has been difficult, however, due to the paucity of known epitopes. We have analyzed the potential of L. major transgenic parasites, expressing the model antigen ovalbumin (OVA), to be presented by antigen-presenting cells to OVA-specific OT-II CD4+ or OT-I CD8+ T cells. Truncated OVA was expressed in L. major as part of a secreted or nonsecreted chimeric protein with L. donovani 3′ nucleotidase (NT-OVA). Dendritic cells (DC) but not macrophages infected with L. major that secreted NT-OVA could prime OT-I T cells to proliferate and release gamma interferon. A diminished T-cell response was observed when DC were infected with parasites expressing nonsecreted NT-OVA or with heat-killed parasites. Inoculation of mice with transgenic parasites elicited the proliferation of adoptively transferred OT-I T cells and their recruitment to the site of infection in the skin. Together, these results demonstrate the possibility of targeting heterologous antigens to specific cellular compartments in L. major and suggest that proteins secreted or released by L. major in infected DC are a major source of peptides for the generation of parasite-specific CD8+ T cells. The ability of L. major transgenic parasites to activate OT-I CD8+ T cells in vivo will permit the analysis of parasite-driven T-cell expansion, differentiation, and recruitment at the clonal level. PMID:16177338

Balance between early life tolerance and sensitization in allergy: dependence on the timing and intensity of prenatal and postnatal allergen exposure of the mother.

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Fusaro, Ana Elisa; de Brito, Cyro Alves; Taniguchi, Eliana Futata; Muniz, Bruno Pacola; Victor, Jefferson Russo; Orii, Noemia Mie; Duarte, Alberto José da Silva; Sato, Maria Notomi

2009-09-01

Allergens can be maternally transferred to the fetus or neonate, though it is uncertain how this initial allergen exposure may impact the development of allergy responses. To evaluate the roles of timing and level of maternal allergen exposure in the early life sensitization of progeny, female BALB/c mice were given ovalbumin (OVA) orally during pregnancy, lactation or weekly at each stage to investigate the immunoglobulin E (IgE) antibody production and cellular responsiveness of their offspring. Exposure to OVA during pregnancy was also evaluated in OVA-specific T-cell receptor (TCR) transgenic (DO11.10) mice. The effect of prenatal antigen exposure on offspring sensitization was dependent on antigen intake, with low-dose OVA inducing tolerance followed by neonatal immunization that was sustained even when pups were immunized when 3 weeks old. These offspring received high levels of transforming growth factor-beta via breastfeeding. High-dose exposure during the first week of pregnancy or perinatal period induced transient inhibition of IgE production following neonatal immunization; although for later immunization IgE production was enhanced in these offspring. Postnatal maternal antigen exposure provided OVA transference via breastfeeding, which consequently induced increased offspring susceptibility to IgE antibody production according to week post-birth. The effect of low-dose maternal exposure during pregnancy was further evaluated using OVA transgenic TCR dams as a model. These progeny presented pronounced entry of CD4(+) T cells into the S phase of the cell cycle with a skewed T helper type 2 response early in life, revealing the occurrence of allergen priming in utero. The balance between tolerance and sensitization depended on the amount and timing of maternal allergen intake during pregnancy.

A combined approach of hollow microneedles and nanocarriers for skin immunization with plasmid DNA encoding ovalbumin

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Pamornpathomkul B

2017-01-01

Full Text Available Boonnada Pamornpathomkul,1 Adisak Wongkajornsilp,2 Wanida Laiwattanapaisal,3 Theerasak Rojanarata,1 Praneet Opanasopit,1 Tanasait Ngawhirunpat1 1Department of Pharmaceutical Technology, Faculty of Pharmacy, Pharmaceutical Development of Green Innovations Group, Silpakorn University, Nakhon Pathom, 2Department of Pharmacology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, 3Department of Clinical Chemistry, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok, Thailand Abstract: The aim of this study was to investigate the use of different types of microneedles (MNs and nanocarriers for in vitro skin permeation and in vivo immunization of plasmid DNA encoding ovalbumin (pOVA. In vitro skin permeation studies indicated that hollow MNs had a superior enhancing effect on skin permeation compared with solid MN patches, electroporation (EP patches, the combination of MN and EP patches, and untreated skin. Upon using hollow MNs combined with nanocarriers for pOVA delivery, the skin permeation was higher than for the delivery of naked pOVA, as evidenced by the increased amount of pOVA in Franz diffusion cells and immunoglobulin G (IgG antibody responses. When the hollow MNs were used for the delivery of nanocarrier:pOVA complexes into the skin of mice, they induced a stronger IgG immune response than conventional subcutaneous (SC injections. In addition, immunization of mice with the hollow MNs did not induce signs of skin infection or pinpoint bleeding. Accordingly, the hollow MNs combined with a nanocarrier delivery system is a promising approach for delivering pOVA complexes to the skin for promoting successful immunization. Keywords: hollow microneedle, solid microneedle, electroporation, plasmid DNA encoding ovalbumin, skin immunization, nanocarrier

An Archaeosome-Adjuvanted Vaccine and Checkpoint Inhibitor Therapy Combination Significantly Enhances Protection from Murine Melanoma

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Felicity C. Stark

2017-10-01

Full Text Available Archaeosomes constitute archaeal lipid vesicle vaccine adjuvants that evoke a strong CD8+ T cell response to antigenic cargo. Therapeutic treatment of murine B16-ovalbumin (B16-OVA melanoma with archaeosome-OVA eliminates small subcutaneous solid tumors; however, they eventually resurge despite an increased frequency of circulating and tumor infiltrating OVA-CD8+ T cells. Herein, a number of different approaches were evaluated to improve responses, including dose number, interval, and the combination of vaccine with checkpoint inhibitors. Firstly, we found that tumor protection could not be enhanced by repetitive and/or delayed boosting to maximize the CD8+ T cell number and/or phenotype. The in vivo cytotoxicity of vaccine-induced OVA-CD8+ T cells was impaired in tumor-bearing mice. Additionally, tumor-infiltrating OVA-CD8+ T cells had an increased expression of programmed cell death protein-1 (PD-1 compared to other organ compartments, suggesting impaired function. Combination therapy of tumor-bearing mice with the vaccine archaeosome-OVA, and α-CTLA-4 administered concurrently as well as α-PD-1 and an α-PD-L1 antibody administered starting 9 days after tumor challenge given on a Q3Dx4 schedule (days 9, 12, 15 and 18, significantly enhanced survival. Following multi-combination therapy ~70% of mice had rapid tumor recession, with no detectable tumor mass after >80 days in comparison to a median survival of 17–22 days for untreated or experimental groups receiving single therapies. Overall, archaeosomes offer a powerful platform for delivering cancer antigens when used in combination with checkpoint inhibitor immunotherapies.

Glutamate receptor antibodies directed against AMPA receptors subunit 3 peptide B (GluR3B) can be produced in DBA/2J mice, lower seizure threshold and induce abnormal behavior.

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Ganor, Yonatan; Goldberg-Stern, Hadassa; Cohen, Ran; Teichberg, Vivian; Levite, Mia

2014-04-01

Anti-GluR3B antibodies (GluR3B Ab's), directed against peptide B/aa372-395 of GluR3 subunit of glutamate/AMPA receptors, are found in ∼35% of epilepsy patients, activate glutamate/AMPA receptors, evoke ion currents, kill neurons and damage the brain. We recently found that GluR3B Ab's also associate with neurological/psychiatric/behavioral abnormalities in epilepsy patients. Here we asked if GluR3B Ab's could be produced in DBA/2J mice, and also modulate seizure threshold and/or cause behavioral/motor impairments in these mice. DBA/2J mice were immunized with the GluR3B peptide in Complete Freund's Adjuvant (CFA), or with controls: ovalbumin (OVA), CFA, or phosphate-buffer saline (PBS). GluR3B Ab's and OVA Ab's were tested. Seizures were induced in all mice by the chemoconvulsant pentylenetetrazole (PTZ) at three time points, each time with less PTZ to avoid non-specific death. Behavior was examined in Open-Field, RotaRod and Grip tests. GluR3B Ab's were produced only in GluR3B-immunized mice, while OVA Ab's were produced only in OVA-immunized mice, showing high Ab's specificity. In GluR3B Ab's negative mice, seizure severity scores and percentages of animals developing generalized seizures declined in response to decreasing PTZ doses. In contrast, both parameters remained unchanged/high in the GluR3B Ab's positive mice, showing that these mice were more susceptible to seizures. The seizure scores associated significantly with the GluR3B Ab's levels. GluR3B Ab's positive mice were also more anxious in Open-Field test, fell faster in RotaRod test, and fell more in Grip test, compared to all the control mice. GluR3B Ab's are produced in DBA/2J mice, facilitate seizures and induce behavioral/motor impairments. This animal model can therefore serve for studying autoimmune epilepsy and abnormal behavior mediated by pathogenic anti-GluR3B Ab's. Copyright © 2014 Elsevier Ltd. All rights reserved.

Isothermal Recombinase Polymerase amplification (RPA) of Schistosoma haematobium DNA and oligochromatographic lateral flow detection.

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Rosser, A; Rollinson, D; Forrest, M; Webster, B L

2015-09-04

Accurate diagnosis of urogenital schistosomiasis is vital for surveillance/control programs. Amplification of schistosome DNA in urine by PCR is sensitive and specific but requires infrastructure, financial resources and skilled personnel, often not available in endemic areas. Recombinase Polymerase Amplification (RPA) is an isothermal DNA amplification/detection technology that is simple, rapid, portable and needs few resources. Here a Schistosoma haematobium RPA assay was developed and adapted so that DNA amplicons could be detected using oligochromatographic Lateral Flow (LF) strips. The assay successfully amplified S. haematobium DNA at 30-45 °C in 10 mins and was sensitive to a lower limit of 100 fg of DNA. The assay was also successful with the addition of crude urine, up to 5% of the total reaction volume. Cross amplification occurred with other schistosome species but not with other common urine microorganisms. The LF-RPA assay developed here can amplify and detect low levels of S. haematobium DNA. Reactions are rapid, require low temperatures and positive reactions are interpreted using lateral flow strips, reducing the need for infrastructure and resources. This together with an ability to withstand inhibitors within urine makes RPA a promising technology for further development as a molecular diagnostic tool for urogenital schistosomiasis.

Natural CD8{sup +}25{sup +} regulatory T cell-secreted exosomes capable of suppressing cytotoxic T lymphocyte-mediated immunity against B16 melanoma

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Xie, Yufeng; Zhang, Xueshu; Zhao, Tuo; Li, Wei; Xiang, Jim, E-mail: jim.xiang@saskcancer.ca

2013-08-16

Highlights: •CD8{sup +}25{sup +} regulatory T cells secrete tolerogenic exosomes. •CD8{sup +}25{sup +} regulatory T cell-derived exosomes exhibit immunosuppressive effect. •CD8{sup +}25{sup +} regulatory T cell-derived exosomes inhibit antitumor immunity. -- Abstract: Natural CD4{sup +}25{sup +} and CD8{sup +}25{sup +} regulatory T (Tr) cells have been shown to inhibit autoimmune diseases. Immune cells secrete exosomes (EXOs), which are crucial for immune regulation. However, immunomodulatory effect of natural Tr cell-secreted EXOs is unknown. In this study, we purified natural CD8{sup +}25{sup +} Tr cells from C57BL/6 mouse naive CD8{sup +} T cells, and in vitro amplified them with CD3/CD28 beads. EXOs (EXO{sub Tr}) were purified from Tr cell’s culture supernatants by differential ultracentrifugation and analyzed by electron microscopy, Western blot and flow cytometry. Our data showed that EXO{sub Tr} had a “saucer” or round shape with 50–100 nm in diameter, contained EXO-associated markers LAMP-1 and CD9, and expressed natural Tr cell markers CD25 and GITR. To assess immunomodulatory effect, we i.v. immunized C57BL/6 mice with ovalbumin (OVA)-pulsed DCs (DC{sub OVA}) plus Tr cells or EXO{sub Tr}, and then assessed OVA-specific CD8{sup +} T cell responses using PE-H-2K{sup b}/OVA tetramer and FITC-anti-CD8 antibody staining by flow cytometry and antitumor immunity in immunized mice with challenge of OVA-expressing BL6–10{sub OVA} melanoma cells. We demonstrated that DC{sub OVA}-stimulated CD8{sup +} T cell responses and protective antitumor immunity significantly dropped from 2.52% to 1.08% and 1.81% (p < 0.05), and from 8/8 to 2/8 and 5/8 mice DC{sub OVA} (p < 0.05) in immunized mice with co-injection of Tr cells and EXO{sub Tr}, respectively. Our results indicate that natural CD8{sup +}25{sup +} Tr cell-released EXOs, alike CD8{sup +}25{sup +} Tr cells, can inhibit CD8{sup +} T cell responses and antitumor immunity. Therefore, EXOs derived from

Citrus tachibana Leaves Ethanol Extract Alleviates Airway Inflammation by the Modulation of Th1/Th2 Imbalance via Inhibiting NF-κB Signaling and Histamine Secretion in a Mouse Model of Allergic Asthma.

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Bui, Thi Tho; Piao, Chun Hua; Kim, Soo Mi; Song, Chang Ho; Shin, Hee Soon; Lee, Chang-Hyun; Chai, Ok Hee

2017-07-01

Asthma is a chronic inflammatory disease of bronchial airway, which is characterized by chronic airway inflammation, airway edema, goblet cell hyperplasia, the aberrant production of the Th2 cytokines, and eosinophil infiltration in the lungs. In this study, the therapeutic effect and the underlying mechanism of Citrus tachibana leaves ethanol extract (CTLE) in the ovalbumin (OVA)-induced allergic asthma and compound 48/80-induced anaphylaxis were investigated. Oral administration of CTLE inhibited OVA-induced asthmatic response by reducing airway inflammation, OVA-specific IgE and IgG1 levels, and increasing OVA-specific IgG2a levels. CTLE restored Th1/Th2 balance through an increase in Th2 cytokines tumor necrosis factor-α, interleukin (IL)-4, and IL-6 and decreases in Th1 cytokines interferon-γ and IL-12. Furthermore, CTLE inhibited the total level of NF-κB and the phosphorylation of IκB-α and NF-κB by OVA. In addition, CTLE dose-dependently inhibited compound 48/80-induced anaphylaxis via blocking histamine secretion from mast cells. The anti-inflammatory mechanism of CTLE may involve the modulation of Th1/Th2 imbalance via inhibiting the NF-κB signaling and histamine secretion. Taken together, we suggest that CTLE could be used as a therapeutic agent for patients with Th2-mediated or histamine-mediated allergic asthma.

Objetos virtuais de aprendizagem: contribuições para o processo de aprendizagem em saúde e enfermagem Objetos virtuales de aprendizaje: contribuciones para el proceso de aprendizaje en salud y enfermería Virtual learning objects: contributions to the learning process in health and nursing

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Ana Graziela Alvarez

2011-01-01

Full Text Available OBJETIVO: Evidenciar as contribuições da aplicação de Objetos Virtuais de Aprendizagem (OVAs para o processo de aprendizagem em saúde e enfermagem. MÉTODOS: Estudo de revisão sistemática realizada nas bases de dados PUBMED/MEDLINE, SCOPUS, CINAHL e ISI Web of Knowledge. Foram analisados 13 estudos, publicados no idioma inglês no período de 2004 a 2008. RESULTADOS: Predominaram as pesquisas sobre OVAs desenvolvidas com enfoque em pacientes (50%, estudantes (38,4% e profissionais de saúde (7,1%. Quanto aos níveis de evidência 30,8% dos estudos foram classificados como nível II e nível III-1, respectivamente e 30,4% de nível IV. CONCLUSÃO: Os OVAs contribuíram significativamente para o aumento do conhecimento e aprendizagem em pacientes, alunos e cuidadores, constituindo uma promissora perspectiva para educação em saúde e enfermagem.OBJETIVO: Evidenciar las contribuciones de la aplicación de Objetos Virtuales de Aprendizaje (OVAs para el proceso de aprendizaje en salud y enfermería. MÉTODOS: Estudio de revisión sistemática realizada en las bases de datos PUBMED/MEDLINE, SCOPUS, CINAHL e ISI Web of Knowledge. Fueron analizados 13 estudios, publicados en el idioma inglés en el período de 2004 a 2008. RESULTADOS: Predominaron las investigaciones sobre OVAs desarrolladas con enfoque en pacientes (50%, estudiantes (38,4% y profesionales de salud (7,1%. En cuanto a los niveles de evidencia el 30,8% de los estudios fueron clasificados como nivel II y nivel III-1, respectivamente y el 30,4% como nivel IV. CONCLUSIÓN: Los OVAs contribuyeron significativamente en el aumento del conocimiento y aprendizaje en pacientes, alumnos y cuidadores, constituyendo una prometedora perspectiva para la educación en salud y en enfermería.OBJECTIVE: To highlight the contributions of the application of Virtual Learning Objects (OVAs for the learning process in health and nursing. METHODS: A systematic review was conducted using the databases of

[Effect of health education intervention in schools of Yanrui Town, Yushan County].

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Zhou, Xing; Chen, Rao-Sheng; Zheng, De-Ren; Li, Jian-Ren; Cheng, Xiao-Bo; Ao, Jian-Qiu; Liu, He-Xing

2013-12-01

To evaluate the effect of a new mode of health education in schools. In the Zhaiqian Primary School, Yanrui Town, Yushan County in a hilly schistosomiasis endemic area, a new mode of health education intervention, i. e. "rewards and punishment + advise others by using one's experience + teachers' participation" was carried out, and the knowledge, attitude and practice of schistosomiasis prevention of the pupils, and the schistosome infection rates of the pupils were investigated and the results were analyzed and compared before and after the intervention. Among 204 pupils investigated, the awareness rate of schistosomiasis prevention knowledge increased from 26.47% before the intervention to 86.76% and 99.51% one and two years after the intervention, respectively; the rate of correct attitude increased from 17.04% to 73.04% and 100%, respectively; the rate of the infested water contact decreased from 83.33% to 26.96% and 0, respectively; the schistosome infection rate decreased from 2.94% to 0.49% and 0, respectively. The health education of schistosomiasis prevention in schools is necessary, and the new mode of health education, "rewards and punishment + advise others by using one's experience + teachers' participation" is effective in the prevention from schistosome infection in pupils.

The potential role of Morus alba leaves extract on the brain of mice infected with Schistosoma mansoni.

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Bauomy, Amira A

2014-01-01

Schistosomiasis is a neglected tropical disease which is associated with neuropsychiatric and neuropathological disorders. Herein, the main goal of the presented work is to investigate the effect of Morus alba leaves extract in mice brain infected with Schistosoma mansoni. Since, the resistance of Schistosomes to antischistosomal drug (praziquantel) has been examined, schistosomiasis induced brain oxidative stress as evidenced by the decrease of glutathione level, total antioxidant capacity and the activity of catalase significantly, while a significant elevation in the levels of nitrite/nitrate and malondialdhyde. In addition, the infection resulted in neurochemical disturbances, the main inhibitory amino acid, γ- aminobutyric acid level was decreased. In contrast, the level of chloride ions and acetylcholine esterase activity were significantly increased. Moreover, the histopathological section showed some impairments in the brain. The treatment with Morus alba leaves extract ameliorated the induced disturbances in schistosome-infected mice where the levels of non-enzymatic and enzymatic antioxidants were elevated. On the other hand, the levels of nitrite/nitrate and malondialdhyde were significantly reduced. Likewise, treatment of mice with Morus alba leaves extract improved the altered levels of γ- aminobutyric acid level and chloride ion. Also, it improved the recorded impairments of the histopathological section in the brain of schistosome infected mice.

Dianthus superbus fructus suppresses airway inflammation by downregulating of inducible nitric oxide synthase in an ovalbumin-induced murine model of asthma

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2012-01-01

Background Dianthus superbus has long been used as a herbal medicine in Asia and as an anti-inflammatory agent. In this study, we evaluated the anti-inflammatory effects of Dianthus superbus fructus ethanolic extract (DSE) on Th2-type cytokines, eosinophil infiltration, and other factors in an ovalbumin (OVA)-induced murine asthma model. To study the possible mechanism of the anti-inflammatory effect of DSE, we also evaluated the expression of inducible nitric oxide synthase (iNOS) in the respiratory tract. Methods Mice were sensitized on days 0 and 14 by intraperitoneal injection of OVA. On days 21, 22 and 23 after initial sensitization, mice received an airway challenge with OVA for 1 h using an ultrasonic nebulizer. DSE was applied 1 h prior to OVA challenge. Mice were administered DSE orally at doses of 100 mg/kg or 200 mg/kg once daily from day 18 to 23. Bronchoalveolar lavage fluid (BALF) was collected 48 h after the final OVA challenge. Levels of interleukin (IL)-4, IL-13 and eotaxin in BALF were measured using enzyme-linked immunosorbent assays (ELISAs). Lung tissue sections were stained with hematoxylin and eosin for assessment of cell infiltration and mucus production with periodic acid shift staining, in conjunction with ELISA and western blot analyses for iNOS expression. Results DSE significantly reduced the levels of IL-4, IL-13, eotaxin, and immunoglobulin (Ig) E, number of inflammatory cells in BALF, and inflammatory cell infiltration and mucus production in the respiratory tract. DSE also attenuated the overexpression of iNOS protein induced by OVA challenge. Conclusion Our results suggest that DSE effectively protects against allergic airway inflammation by downregulating of iNOS expression and that DSE has potential as a therapeutic agent for allergic asthma. PMID:23110404

Dietary Fructo-Oligosaccharides Attenuate Early Activation of CD4+ T Cells Which Produce both Th1 and Th2 Cytokines in the Intestinal Lymphoid Tissues of a Murine Food Allergy Model.

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Tsuda, Masato; Arakawa, Haruka; Ishii, Narumi; Ubukata, Chihiro; Michimori, Mana; Noda, Masanari; Takahashi, Kyoko; Kaminogawa, Shuichi; Hosono, Akira

2017-01-01

Fructo-oligosaccharides (FOS) are prebiotic agents with immunomodulatory effects involving improvement of the intestinal microbiota and metabolome. In this study, we investigated the cellular mechanisms through which FOS modulate intestinal antigen-specific CD4+ T cell responses in food allergy, using OVA23-3 mice. OVA23-3 mice were fed an experimental diet containing either ovalbumin (OVA) or OVA and FOS for 1 week. Body weight and mucosal mast cell protease 1 in the serum were measured as the indicator of intestinal inflammation. Single-cell suspensions were prepared from intestinal and systemic lymphoid tissues for cellular analysis. Cytokine production was measured by ELISA. Activation markers and intracellular cytokines in CD4+ T cells were analyzed by flow cytometry. Activated CD4+ T cells were purified to examine cytokine production. Dietary intake of FOS provided moderate protection from the intestinal inflammation induced by the OVA-containing diet. FOS significantly reduced food allergy-induced Th2 cytokine responses in intestinal tissues but not in systemic tissues. FOS decreased OVA diet-induced IFN-γ+IL-4+ double-positive CD4+ T cells and early-activated CD45RBhighCD69+CD4+ T cells in the mesenteric lymph nodes. Furthermore, we confirmed that these CD45RBhighCD69+CD4+ T cells are able to produce high levels of IFN-γ and moderate level of IL-4, IL-10, and IL-13. Dietary intake of FOS during the development of food allergy attenuates the induction of intestinal Th2 cytokine responses by regulating early activation of naïve CD4+ T cells, which produce both Th1 and Th2 cytokines. Our results suggest FOS might be a potential food agent for the prevention of food allergy by modulating oral sensitization to food antigens. © 2017 S. Karger AG, Basel.

Study of the allergenic potential of Bacillus thuringiensis Cry1Ac toxin following intra-gastric administration in a murine model of food-allergy.

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Santos-Vigil, Karla I; Ilhuicatzi-Alvarado, Damaris; García-Hernández, Ana L; Herrera-García, Juan S; Moreno-Fierros, Leticia

2018-06-07

Cry1Ac toxin, from Bacillus thuringiensis, is widely used as a biopesticide and expressed in genetically modified (GM) plants used for human and animal consumption. Since Cry1Ac is also immunogenic and able to activate macrophages, it is crucial to thoroughly evaluate the immunological effects elicited after intra-gastric administration. The allergenic potential of purified Cry1Ac was assessed and compared with that induced in a murine model of food-allergy to ovalbumin (OVA), in which animals are sensitized with the adjuvant Cholera toxin (CT). Mice were weekly intragastrically administered with: i) vehicle phosphate-buffered saline (PBS), ii) OVA, iii) OVA plus CT iv) Cry1Ac or v) OVA plus Cry1Ac. Seven weeks after, mice were intragastrically challenged and allergic reactions along with diverse allergy related immunological parameters were evaluated at systemic and intestinal level. The groups immunized with, Cry1Ac, OVA/Cry1Ac or OVA/CT developed moderate allergic reactions, induced significant IgE response and increased frequencies of intestinal granulocytes, IgE+ eosinophils and IgE+ lymphocytes. These same groups also showed colonic lymphoid hyperplasia, notably in humans, this has been associated with food allergy and intestinal inflammation. Although the adjuvant and allergenic potential of CT were higher than the effects of Cry1Ac, the results show that applied intra-gastrically at 50 μg doses, Cry1Ac is immunogenic, moderately allergenic and able to provoke intestinal lymphoid hyperplasia. Moreover, Cry1Ac is also able to induce anaphylaxis, since when mice were intragastrically sensitized with increasing doses of Cry1Ac, with every dose tested, a significant drop in rectal temperature was recorded after intravenous challenge. Copyright © 2018 Elsevier B.V. All rights reserved.

Functional transforming growth factor-β receptor type II expression by CD4+ T cells in Peyer's patches is essential for oral tolerance induction.

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Rebekah S Gilbert

Full Text Available Our previous studies have shown that Peyer's patches (PPs play a key role in the induction of oral tolerance. Therefore, we hypothesized that PPs are an important site for Transforming Growth Factor (TGF-β signaling and sought to prove that this tissue is of importance in oral tolerance induction. We found that expression of TGF-β type II receptor (TGFβRII by CD4(+ T cells increases and persists in the PPs of normal C57BL/6 mice after either high- or low-dose feeding of OVA when compared to mesenteric lymph nodes (MLNs and spleen. Approximately one-third of these TGFβRII(+ CD4(+ T cells express the transcription factor Foxp3. Interestingly, the number of TGFβRII(+ CD4(+ T cells in PPs decreased when OVA-fed mice were orally challenged with OVA plus native cholera toxin (CT. In contrast, numbers of TGFβRII(+ CD4(+ T cells were increased in the intestinal lamina propria (iLP of these challenged mice. Further, these PP CD4(+ TGFβRII(+ T cells upregulated Foxp3 within 2 hours after OVA plus CT challenge. Mice fed PBS and challenged with OVA plus CT did not reveal any changes in TGFβRII expression by CD4(+ T cells. In order to test the functional property of TGFβRII in the induction of oral tolerance, CD4dnTGFβRII transgenic mice, in which TGFβRII signaling is abrogated from all CD4(+ T cells, were employed. Importantly, these mice could not develop oral tolerance to OVA. Our studies show a critical, dose-independent, role for TGFβRII expression and function by CD4(+ T cells in the gut-associated lymphoid tissues, further underlining the vital role of PPs in oral tolerance.

Maternal immunization with ovalbumin prevents neonatal allergy development and up-regulates inhibitory receptor FcγRIIB expression on B cells

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Duarte Alberto JS

2010-03-01

Full Text Available Abstract Background Preconception allergen immunization prevents neonatal allergen sensitization in mice by a complex interaction between regulatory cells/factors and antibodies. The present study assessed the influence of maternal immunization with ovalbumin (OVA on the immune response of 3 day-old and 3 week-old offspring immunized or non-immunized with OVA and evaluated the effect of IgG treatment during fetal development or neonatal period. Results Maternal immunization with OVA showed increased levels of FcγRIIb expression in splenic B cells of neonates, which were maintained for up to 3 weeks and not affected by additional postnatal OVA immunization. Maternal immunization also exerted a down-modulatory effect on both IL-4 and IFN-γ-secreting T cells and IL-4 and IL-12- secreting B cells. Furthermore, immunized neonates from immunized mothers showed a marked inhibition of antigen-specifc IgE Ab production and lowered Th2/Th1 cytokine levels, whereas displaying enhanced FcγRIIb expression on B cells. These offspring also showed reduced antigen-specific proliferative response and lowered B cell responsiveness. Moreover, in vitro evaluation revealed an impairment of B cell activation upon engagement of B cell antigen receptor by IgG from OVA-immunized mice. Finally, in vivo IgG transference during pregnancy or breastfeeding revealed that maternal Ab transference was able to increase regulatory cytokines, such as IL-10, in the prenatal stage; yet only the postnatal treatment prevented neonatal sensitization. None of the IgG treatments induced immunological changes in the offspring, as it was observed for those from OVA-immunized mothers. Conclusion Maternal immunization upregulates the inhibitory FcγRIIb expression on offspring B cells, avoiding skewed Th2 response and development of allergy. These findings contribute to the advancement of prophylactic strategies to prevent allergic diseases in early life.

Induction of immunity to antigens expressed by recombinant adeno-associated virus depends on the route of administration.

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Brockstedt, D G; Podsakoff, G M; Fong, L; Kurtzman, G; Mueller-Ruchholtz, W; Engleman, E G

1999-07-01

Recombinant adeno-associated virus (rAAV) is a replication-defective parvovirus which is being explored as a vector for gene therapy because of its broad host range, excellent safety profile, and durable transgene expression in infected hosts. rAAV has also been reported by several groups to induce little or no immune response to its encoded transgene products. In this study we examined the immunogenicity of rAAV by studying the immune response of C57BL/6 mice to a single dose of rAAV-encoding ovalbumin (AAV-Ova) administered by a variety of routes. Mice injected with AAV-Ova intraperitoneally (ip), intravenously, or subcutaneously developed potent ovalbumin-specific cytotoxic T lymphocytes (CTL) as well as anti-ovalbumin antibodies and antibodies to AAV. In contrast, mice injected with AAV-Ova intramuscularly developed a humoral response to the virus and the transgene but minimal ovalbumin-specific CTLs. The induced CTL response after ip administration of AAV-Ova protected mice against a subsequent tumor challenge with an ovalbumin-transfected B16 melanoma cell line. Studies of the mechanism by which AAV-Ova induces CTL confirmed that the virus delivers the transgene product into the classical MHC class I pathway of antigen processing. Mice that previously had been exposed to rAAV vectors failed to develop ovalbumin-specific CTL following administration of AAV-Ova. Analysis of these mice revealed the presence of circulating anti-AAV antibodies that blocked rAAV transduction in vitro and inhibited CTL induction in vivo. These results suggest a possible role for rAAV in the immunotherapy of malignancies and viral infections, although induced antibody responses to AAV may limit its ability to be administered for repeated vaccinations. Copyright 1999 Academic Press.

Novel T-cell epitopes of ovalbumin in BALB/c mouse: Potential for peptide-immunotherapy

International Nuclear Information System (INIS)

Yang, Marie; Mine, Yoshinori

2009-01-01

The identification of food allergen T-cell epitopes provides a platform for the development of novel immunotherapies. Despite extensive knowledge of the physicochemical properties of hen ovalbumin (OVA), a major egg allergen, the complete T-cell epitope map of OVA has surprisingly not been defined in the commonly used BALB/c mouse model. In this study, spleen cells obtained from OVA-sensitized mice were incubated in the presence of 12-mer overlapping synthetic peptides, constructed using the SPOTS synthesis method. Proliferative activity was assessed by 72-h in vitro assays with use of the tetrazolium salt WST-1 and led to identification of four mitogenic sequences, i.e., A39R50, S147R158, K263E274, and A329E340. ELISA analyses of interferon (IFN)-γ and interleukin (IL)-4 productions in cell culture supernatants upon stimulation with increasing concentrations of peptides confirmed their immunogenicity. Knowledge of the complete T-cell epitope map of OVA opens the way to a number of experimental investigations, including the exploration of peptide-based immunotherapy.

Treatment for Schistosoma japonicum, reduction of intestinal parasite load, and cognitive test score improvements in school-aged children.

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Amara E Ezeamama

deworming and simultaneous control for schistosome and STH infections could improve children's ability to take advantage of educational opportunities in helminth-endemic regions.

Immunotherapy with Dendritic Cells Modified with Tumor-Associated Antigen Gene Demonstrates Enhanced Antitumor Effect Against Lung Cancer

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Tao Jiang

2017-04-01

Full Text Available BACKGROUND: Immunotherapy using dendritic cell (DC vaccine has the potential to overcome the bottleneck of cancer therapy. METHODS: We engineered Lewis lung cancer cells (LLCs and bone marrow–derived DCs to express tumor-associated antigen (TAA ovalbumin (OVA via lentiviral vector plasmid encoding OVA gene. We then tested the antitumor effect of modified DCs both in vitro and in vivo. RESULTS: The results demonstrated that in vitro modified DCs could dramatically enhance T-cell proliferation (P < .01 and killing of LLCs than control groups (P < .05. Moreover, modified DCs could reduce tumor size and prolong the survival of LLC tumor-bearing mice than control groups (P < .01 and P < .01, respectively. Mechanistically, modified DCs demonstrated enhanced homing to T-cell–rich compartments and triggered more naive T cells to become cytotoxic T lymphocytes, which exhibited significant infiltration into the tumors. Interestingly, modified DCs also markedly reduced tumor cells harboring stem cell markers in mice (P < .05, suggesting the potential role on cancer stem-like cells. CONCLUSION: These findings suggested that DCs bioengineered with TAA could enhance antitumor effect and therefore represent a novel anticancer strategy that is worth further exploration.

Why reinvent the wheel? Lessons in schistosomiasis control from the past.

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Clive Shiff

2017-10-01

Full Text Available Schistosomiasis has been of concern to local health authorities for most of the last century, and in spite of a lack of effective chemotherapy, the disease was dealt with quite effectively in many endemic countries by snail control and environmental management [1]. Much of this work was reported in journals prior to the electronic era but, sadly, seems to have been subsequently ignored. For many years, there followed a global hiatus on schistosomiasis control, and much of the local expertise was lost, but many things have changed more recently, mainly with the advent of generic and affordable praziquantel. With the increased availability of this drug, there has been an increasing interest in readdressing schistosomes as well as other neglected tropical diseases (NTDs. The strategic approach for this had been based almost exclusively on chemotherapy. Recently, however, questions arose about this strategy with evidence that chemotherapy alone was not succeeding [2]. Additional strategies were needed, and the "Towards Elimination of Schistosomiasis" (TES 2017 Conference in Cameroon stressed an integrated PHASE strategy. This was in line with the WHO-NTD and WHO-AFRO 2014-2020 Regional Strategy on NTDs and directed emphasis on transmission control. Subsequently, this emphasis was discussed in a comprehensive review [3] that stressed the importance of such additions to any elimination programme. In reality, this means focusing on the aquatic snail hosts where and when transmission occurs, defining other risk factors such as water contact and latrine design and identifying improved sanitation and health education as essential components for elimination. For schistosomiasis reduction during the mid-20th century, transmission control was used extensively, but these facts are not well reported. Recent reviews have attempted to cover previous research [4,5], but sadly, they have left major knowledge gaps, particularly from Africa. These omissions also

Why reinvent the wheel? Lessons in schistosomiasis control from the past.

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Shiff, Clive

2017-10-01

Schistosomiasis has been of concern to local health authorities for most of the last century, and in spite of a lack of effective chemotherapy, the disease was dealt with quite effectively in many endemic countries by snail control and environmental management [1]. Much of this work was reported in journals prior to the electronic era but, sadly, seems to have been subsequently ignored. For many years, there followed a global hiatus on schistosomiasis control, and much of the local expertise was lost, but many things have changed more recently, mainly with the advent of generic and affordable praziquantel. With the increased availability of this drug, there has been an increasing interest in readdressing schistosomes as well as other neglected tropical diseases (NTDs). The strategic approach for this had been based almost exclusively on chemotherapy. Recently, however, questions arose about this strategy with evidence that chemotherapy alone was not succeeding [2]. Additional strategies were needed, and the "Towards Elimination of Schistosomiasis" (TES) 2017 Conference in Cameroon stressed an integrated PHASE strategy. This was in line with the WHO-NTD and WHO-AFRO 2014-2020 Regional Strategy on NTDs and directed emphasis on transmission control. Subsequently, this emphasis was discussed in a comprehensive review [3] that stressed the importance of such additions to any elimination programme. In reality, this means focusing on the aquatic snail hosts where and when transmission occurs, defining other risk factors such as water contact and latrine design and identifying improved sanitation and health education as essential components for elimination. For schistosomiasis reduction during the mid-20th century, transmission control was used extensively, but these facts are not well reported. Recent reviews have attempted to cover previous research [4,5], but sadly, they have left major knowledge gaps, particularly from Africa. These omissions also occurred in a recent

Serotonin Signaling in Schistosoma mansoni: A Serotonin–Activated G Protein-Coupled Receptor Controls Parasite Movement

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Rashid, Mohammed; Ribeiro, Paula

2014-01-01

Serotonin is an important neuroactive substance in all the parasitic helminths. In Schistosoma mansoni, serotonin is strongly myoexcitatory; it potentiates contraction of the body wall muscles and stimulates motor activity. This is considered to be a critical mechanism of motor control in the parasite, but the mode of action of serotonin is poorly understood. Here we provide the first molecular evidence of a functional serotonin receptor (Sm5HTR) in S. mansoni. The schistosome receptor belongs to the G protein-coupled receptor (GPCR) superfamily and is distantly related to serotonergic type 7 (5HT7) receptors from other species. Functional expression studies in transfected HEK 293 cells showed that Sm5HTR is a specific serotonin receptor and it signals through an increase in intracellular cAMP, consistent with a 5HT7 signaling mechanism. Immunolocalization studies with a specific anti-Sm5HTR antibody revealed that the receptor is abundantly distributed in the worm's nervous system, including the cerebral ganglia and main nerve cords of the central nervous system and the peripheral innervation of the body wall muscles and tegument. RNA interference (RNAi) was performed both in schistosomulae and adult worms to test whether the receptor is required for parasite motility. The RNAi-suppressed adults and larvae were markedly hypoactive compared to the corresponding controls and they were also resistant to exogenous serotonin treatment. These results show that Sm5HTR is at least one of the receptors responsible for the motor effects of serotonin in S. mansoni. The fact that Sm5HTR is expressed in nerve tissue further suggests that serotonin stimulates movement via this receptor by modulating neuronal output to the musculature. Together, the evidence identifies Sm5HTR as an important neuronal protein and a key component of the motor control apparatus in S. mansoni. PMID:24453972

Artificial sweeteners and mixture of food additives cause to break oral tolerance and induce food allergy in murine oral tolerance model for food allergy.

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Yamashita, H; Matsuhara, H; Miotani, S; Sako, Y; Matsui, T; Tanaka, H; Inagaki, N

2017-09-01

Processed foods are part of daily life. Almost all processed foods contain food additives such as sweeteners, preservatives and colourants. From childhood, it is difficult to avoid consuming food additives. It is thought that oral tolerance for food antigens is acquired during early life. If tolerance fails, adverse immune responses to food proteins may occur. We hypothesized that food additives prevent acquisition of oral tolerance and aimed to verify the safety of food additives. We induced experimental oral tolerance in mice for ovalbumin (OVA), a food antigen, by previous oral treatment with OVA before sensitization with OVA injections. Food additives were administered at the induction of oral tolerance, and food allergy was induced by repeated administration of OVA. Symptoms of food allergy were defined as a change in body temperature and allergic diarrhoea. Saccharin sodium and a mixture of food additives inhibited acquisition of oral tolerance. Hypothermia and allergic diarrhoea with elevation of OVA-specific IgE were induced in the murine model of oral tolerance. Analyses of antigen-presenting cells in mesenteric lymph nodes showed that food additives affected their manner of migration. Additionally, food additives decreased the proportion of CD25 hi regulatory T cells among CD4 + T cells in the mesenteric lymph nodes. A large amount of food additives may prevent acquisition of oral tolerance. Intake of food additives in early life may increase the risk of food allergies. © 2017 John Wiley & Sons Ltd.

Polysaccharides from Ganoderma formosanum function as a Th1 adjuvant and stimulate cytotoxic T cell response in vivo.

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Pi, Chia-Chen; Chu, Ching-Liang; Lu, Chu-Ying; Zhuang, Yu-Jing; Wang, Cheng-Li; Yu, Yao-Hsuan; Wang, Hui-Yi; Lin, Chih-Chung; Chen, Chun-Jen

2014-01-09

The fungus of Ganoderma is a basidiomycete that possesses a variety of pharmacological effects and has been used in traditional Asian medicine for centuries. Ganoderma formosanum is a native Ganoderma species isolated in Taiwan, and we have previously demonstrated that PS-F2, a polysaccharide fraction purified from the submerged culture broth of G. formosanum, exhibits immunostimulatory properties in macrophages. In this study, we further characterized the adjuvant functions of PS-F2. In vitro, PS-F2 stimulated dendritic cells (DCs) to produce proinflammatory cytokines, including TNF-α, interleukin (IL)-6, and IL-12/IL-23 p40. PS-F2 also stimulated DCs to express the maturation markers CD40, CD80, CD86, and MHC class II. In a murine splenocyte culture, PS-F2 treatment resulted in elevated expression of T-bet and interferon (IFN)-γ in T lymphocytes. When used as an adjuvant in vivo with the ovalbumin (OVA) antigen, PS-F2 stimulated OVA-specific antibody production and primed IFN-γ production in OVA-specific T lymphocytes. PS-F2-adjuvated immunization also induced OVA-specific CTLs, which protected mice from a challenge with tumor cells expressing OVA. Collectively, our data show that PS-F2 functions as an adjuvant capable of inducing a Th1-polarized adaptive immune response, which would be useful in vaccines against viruses and tumors. Copyright © 2013 Elsevier Ltd. All rights reserved.

Unlipidated Outer Membrane Protein Omp16 (U-Omp16) from Brucella spp. as Nasal Adjuvant Induces a Th1 Immune Response and Modulates the Th2 Allergic Response to Cow’s Milk Proteins

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Ibañez, Andrés E.; Smaldini, Paola; Coria, Lorena M.; Delpino, María V.; Pacífico, Lucila G. G.; Oliveira, Sergio C.; Risso, Gabriela S.; Pasquevich, Karina A.; Fossati, Carlos Alberto; Giambartolomei, Guillermo H.; Docena, Guillermo H.; Cassataro, Juliana

2013-01-01

The discovery of novel mucosal adjuvants will help to develop new formulations to control infectious and allergic diseases. In this work we demonstrate that U-Omp16 from Brucella spp. delivered by the nasal route (i.n.) induced an inflammatory immune response in bronchoalveolar lavage (BAL) and lung tissues. Nasal co-administration of U-Omp16 with the model antigen (Ag) ovalbumin (OVA) increased the amount of Ag in lung tissues and induced OVA-specific systemic IgG and T helper (Th) 1 immune responses. The usefulness of U-Omp16 was also assessed in a mouse model of food allergy. U-Omp16 i.n. administration during sensitization ameliorated the hypersensitivity responses of sensitized mice upon oral exposure to Cow’s Milk Protein (CMP), decreased clinical signs, reduced anti-CMP IgE serum antibodies and modulated the Th2 response in favor of Th1 immunity. Thus, U-Omp16 could be used as a broad Th1 mucosal adjuvant for different Ag formulations. PMID:23861971

Different effects of deep inspirations on central and peripheral airways in healthy and allergen-challenged mice

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Dahlén Sven-Erik

2008-02-01

Full Text Available Abstract Background Deep inspirations (DI have bronchodilatory and bronchoprotective effects in healthy human subjects, but these effects appear to be absent in asthmatic lungs. We have characterized the effects of DI on lung mechanics during mechanical ventilation in healthy mice and in a murine model of acute and chronic airway inflammation. Methods Balb/c mice were sensitized to ovalbumin (OVA and exposed to nebulized OVA for 1 week or 12 weeks. Control mice were challenged with PBS. Mice were randomly selected to receive DI, which were given twice during the minute before assessment of lung mechanics. Results DI protected against bronchoconstriction of central airways in healthy mice and in mice with acute airway inflammation, but not when OVA-induced chronic inflammation was present. DI reduced lung resistance induced by methacholine from 3.8 ± 0.3 to 2.8 ± 0.1 cmH2O·s·mL-1 in healthy mice and 5.1 ± 0.3 to 3.5 ± 0.3 cmH2O·s·mL-1 in acute airway inflammation (both P P P P P Conclusion We have tested a mouse model of potential value for defining mechanisms and sites of action of DI in healthy and asthmatic human subjects. Our current results point to potent protective effects of DI on peripheral parts of chronically inflamed murine lungs and that the presence of DI may blunt airway hyperreactivity.

Improved efficacy of allergen-specific immunotherapy by JAK inhibition in a murine model of allergic asthma.

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Aguilar-Pimentel, Antonio; Graessel, Anke; Alessandrini, Francesca; Fuchs, Helmut; Gailus-Durner, Valerie; Hrabě de Angelis, Martin; Russkamp, Dennis; Chaker, Adam; Ollert, Markus; Blank, Simon; Gutermuth, Jan; Schmidt-Weber, Carsten B

2017-01-01

Allergen-specific immunotherapy (AIT) is the only curative treatment for type-1 allergies, but sometimes shows limited therapeutic response as well as local and systemic side effects. Limited control of local inflammation and patient symptoms hampers its widespread use in severe allergic asthma. Our aim was to evaluate whether AIT is more effective in suppression of local inflammation if performed under the umbrella of short-term non-specific immunomodulation using a small molecule inhibitor of JAK pathways. In C57BL/6J mice, a model of ovalbumin (OVA)-induced allergic airway inflammation and allergen-specific immunotherapy was combined with the administration of Tofacitinib (TOFA, a FDA-approved JAK inhibitor) from 48 hours prior to 48 hours after therapeutic OVA-injection. The effect of TOFA on human FOXP3+CD4+ T cells was studied in vitro. AIT combined with short-term TOFA administration was significantly more effective in suppressing total cell and eosinophil infiltration into the lung, local cytokine production including IL-1β and CXCL1 and showed a trend for the reduction of IL-4, IL-13, TNF-α and IL-6 compared to AIT alone. Furthermore, TOFA co-administration significantly reduced systemic IL-6, IL-1β and OVA-specific IgE levels and induced IgG1 to the same extent as AIT alone. Additionally, TOFA enhanced the induction of human FOXP3+CD4+ T cells. This proof of concept study shows that JAK inhibition did not inhibit tolerance induction, but improved experimental AIT at the level of local inflammation. The improved control of local inflammation might extend the use of AIT in more severe conditions such as polyallergy, asthma and high-risk patients suffering from mastocytosis or anaphylaxis.

Improved efficacy of allergen-specific immunotherapy by JAK inhibition in a murine model of allergic asthma.

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Antonio Aguilar-Pimentel

Full Text Available Allergen-specific immunotherapy (AIT is the only curative treatment for type-1 allergies, but sometimes shows limited therapeutic response as well as local and systemic side effects. Limited control of local inflammation and patient symptoms hampers its widespread use in severe allergic asthma.Our aim was to evaluate whether AIT is more effective in suppression of local inflammation if performed under the umbrella of short-term non-specific immunomodulation using a small molecule inhibitor of JAK pathways.In C57BL/6J mice, a model of ovalbumin (OVA-induced allergic airway inflammation and allergen-specific immunotherapy was combined with the administration of Tofacitinib (TOFA, a FDA-approved JAK inhibitor from 48 hours prior to 48 hours after therapeutic OVA-injection. The effect of TOFA on human FOXP3+CD4+ T cells was studied in vitro.AIT combined with short-term TOFA administration was significantly more effective in suppressing total cell and eosinophil infiltration into the lung, local cytokine production including IL-1β and CXCL1 and showed a trend for the reduction of IL-4, IL-13, TNF-α and IL-6 compared to AIT alone. Furthermore, TOFA co-administration significantly reduced systemic IL-6, IL-1β and OVA-specific IgE levels and induced IgG1 to the same extent as AIT alone. Additionally, TOFA enhanced the induction of human FOXP3+CD4+ T cells.This proof of concept study shows that JAK inhibition did not inhibit tolerance induction, but improved experimental AIT at the level of local inflammation. The improved control of local inflammation might extend the use of AIT in more severe conditions such as polyallergy, asthma and high-risk patients suffering from mastocytosis or anaphylaxis.

Attrition of schistosomes in an irradiation-attenuated cercarial immunization model of Schistosoma mansoni

International Nuclear Information System (INIS)

Stek, M. Jr.; Dean, D.A.; Clark, S.S.

1981-01-01

The attrition of Schistosoma mansoni challenge worms was studied in irradiation-attenuated cercaria-immunized mice as a function of site and time. The peak recovery of schistosomula from the lungs of immunized mice was delayed 2 days in comparison with non-immunized controls. The difference between the peak recoveries of control and immunized mice accounted for about half of the final attrition observed at the 7-week adult worm stge. Hepatic-mesenteric vein worm recoveries obtained 10 to 42 days after challenge were reduced in most cases at least as much as the 49-day counts. Somewhat higher reductions were observed at 14 to 28 days than at 49 days, confirming the evidence of delayed migration obtained at the lung phase. These findings, coupled with histologic observations, indicate that at least half of the worm elimination attributable to immunization occurs 8 or more days after the challenge infection

Improved injection needles facilitate germline transformation of the buckeye butterfly Junonia coenia.

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Beaudette, Kahlia; Hughes, Tia M; Marcus, Jeffrey M

2014-01-01

Germline transformation with transposon vectors is an important tool for insect genetics, but progress in developing transformation protocols for butterflies has been limited by high post-injection ova mortality. Here we present an improved glass injection needle design for injecting butterfly ova that increases survival in three Nymphalid butterfly species. Using the needles to genetically transform the common buckeye butterfly Junonia coenia, the hatch rate for injected Junonia ova was 21.7%, the transformation rate was 3%, and the overall experimental efficiency was 0.327%, a substantial improvement over previous results in other butterfly species. Improved needle design and a higher efficiency of transformation should permit the deployment of transposon-based genetic tools in a broad range of less fecund lepidopteran species.

Oral Administration of Recombinant Saccharomyces boulardii Expressing Ovalbumin-CPE Fusion Protein Induces Antibody Response in Mice

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Ghasem Bagherpour

2018-04-01

Full Text Available Saccharomyces boulardii, a subspecies of Saccharomyces cerevisiae, is a well-known eukaryotic probiotic with many benefits for human health. In the present study, a recombinant strain of S. boulardii was prepared to use as a potential oral vaccine delivery vehicle. In this sense, a ura3 auxotroph strain of S. boulardii CNCM I-745 (known as S. cerevisiae HANSEN CBS 5926, Yomogi® was generated using CRISPR/Cas9 methodology. Then a gene construct encoding a highly immunogenic protein, ovalbumin (OVA, was prepared and transformed into the ura3- S. boulardii. To facilitate the transport of the recombinant immunogen across the intestinal barrier, a claudin-targeting sequence from Clostridium perfringens enterotoxin (CPE was added to the C-terminus of the expression cassette. The recombinant S. boulardii strain expressing the OVA-CPE fusion protein was then administered orally to a group of mice, and serum IgG and fecal IgA levels were evaluated by ELISA. Our results demonstrated that anti-OVA IgG in serum significantly increased in test group (P < 0.001 compared to control groups (receiving wild type S. boulardii or PBS, and the fecal IgA titer was significantly higher in test group (P < 0.05 than control groups. In parallel, a recombinant S. boulardii strain expressing the similar construct lacking C-terminal CPE was also administered orally. The result showed an increased level of serum IgG in group receiving yeasts expressing the CPE negative construct compared to control groups; however, the fecal IgA levels did not increase significantly. In conclusion, our findings indicated that the yeast S. boulardii, as a delivery vehicle with possible immunomodulatory effects, and c-CPE, as a targeting tag, synergistically assist to stimulate systemic and local immunity. This proposed recombinant S. boulardii system might be useful in the expression of other antigenic peptides, making it as a promising tool for oral delivery of vaccines or therapeutic

O&P (Ova and Parasite) Test

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... unwisely or accidentally drink untreated water or contaminated food. Those who travel outside the U.S., especially to developing nations, may ... parasitic infection? The best way is to avoid food and water ... This is especially true if you travel to emerging nations, where ice in a drink ...

Langerhans cell-like dendritic cells stimulated with an adjuvant direct the development of Th1 and Th2 cells in vivo.

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Matsui, K; Mori, A; Ikeda, R

2015-10-01

It is well known that Langerhans cells (LCs) work as the primary orchestrators in the polarization of immune responses towards a T helper type 1 (Th1) or Th2 milieu. In this study, we attempted to generate LCs from murine bone marrow cells and elicit a Th1- or Th2-prone immune response through the LCs after stimulation with Th1 or Th2 adjuvant. LCs were generated from murine bone marrow cells using granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-4 and transforming growth factor (TGF)-β, and were obtained as I-A(d) positive cells. Mice were primed with Th1/Th2 adjuvant- and ovalbumin (OVA)-pulsed LCs and then given a booster injection of OVA 2 days later via the hind footpad. Five days after the OVA injection, the cytokine response in the draining popliteal lymph nodes was investigated by reverse transcription-polymerase chain reaction (RT-PCR) flow cytometry and enzyme-linked immunosorbent assay (ELISA). The generated LCs expressed typical LC surface markers, E-cadherin and Langerin, and were classified accordingly as LC-like dendritic cells (LDCs). Administration of Th1 adjuvant, cytosine-phosphate-guanosine (CpG)-DNA- and OVA-pulsed LDCs into the hind footpads of mice induced a Th1-prone immune response, as represented by up-regulation of IFN-γ production and down-regulation of IL-4 production in the lymph node cells. Conversely, Th2 adjuvant, histamine-pulsed LDCs induced a Th2-prone immune response, as represented by up-regulation of IL-4 production and down-regulation of IFN-γ production. These results suggest that LDCs may be used as a substitute for LCs and have the ability to induce the development of Th1 and Th2 cells in vivo. Our experimental system would therefore be useful for screening of inhibitors of Th1/Th2 differentiation in order to control allergic disease. © 2015 British Society for Immunology.

Effect of aging on airway remodeling and muscarinic receptors in a murine acute asthma model

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Kang JY

2013-10-01

Full Text Available Ji Young Kang, Sook Young Lee, Chin Kook Rhee, Seung Joon Kim, Soon Seog Kwon, Young Kyoon KimDepartment of Internal Medicine, College of Medicine, Catholic University of Korea, Seoul, KoreaBackground and objectives: The influence of aging on the development of asthma has not been studied thoroughly. The aim of this study was to investigate age-related airway responses involving lung histology and expression of muscarinic receptors in a murine model of acute asthma. Methods: Female BALB/c mice at the ages of 6 weeks and 6, 9, and 12 months were sensitized and challenged with ovalbumin (OVA for 1 month (n = 8–12 per group. We analyzed inflammatory cells and T-helper (Th2 cytokines in bronchoalveolar lavage (BAL fluid and parameters of airway remodeling and expression of muscarinic receptors in lung tissue. Results: Among the OVA groups, total cell and eosinophil numbers in BAL fluid were significantly higher in the older (6-, 9-, and 12-month-old mice than in the young (6-week-old mice. Interleukin (IL 4 (IL-4 concentration increased, but IL-5 and IL-13 concentrations showed a decreased tendency, with age. IL-17 concentration tended to increase with age, which did not reach statistical significance. periodic acid-Schiff (PAS staining area, peribronchial collagen deposition, and area of α-smooth muscle staining were significantly higher in the 6-month older OVA group than in the young OVA group. The expression of the M3 and M2 muscarinic receptors tended to increase and decrease, respectively, with age. Conclusion: The aged mice showed an active and unique pattern not only on airway inflammation, but also on airway remodeling and expression of the muscarinic receptors during the development of acute asthma compared with the young mice. These findings suggest that the aging process affects the pathogenesis of acute asthma and age-specific approach might be more appropriate for better asthma control in a clinical practice.Keywords: aging, asthma

Efficacy of integrated school based de-worming and prompt malaria treatment on helminths -Plasmodium falciparum co-infections: A 33 months follow up study

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Chadukura Vivian

2011-06-01

Full Text Available Abstract Background The geographical congruency in distribution of helminths and Plasmodium falciparum makes polyparasitism a common phenomenon in Sub Saharan Africa. The devastating effects of helminths-Plasmodium co-infections on primary school health have raised global interest for integrated control. However little is known on the feasibility, timing and efficacy of integrated helminths-Plasmodium control strategies. A study was conducted in Zimbabwe to evaluate the efficacy of repeated combined school based antihelminthic and prompt malaria treatment. Methods A cohort of primary schoolchildren (5-17 years received combined Praziquantel, albendazole treatment at baseline, and again during 6, 12 and 33 months follow up surveys and sustained prompt malaria treatment. Sustained prompt malaria treatment was carried out throughout the study period. Children's infection status with helminths, Plasmodium and helminths-Plasmodium co-infections was determined by parasitological examinations at baseline and at each treatment point. The prevalence of S. haematobium, S. mansoni, STH, malaria, helminths-Plasmodium co-infections and helminths infection intensities before and after treatment were analysed. Results Longitudinal data showed that two rounds of combined Praziquantel and albendazole treatment for schistosomiasis and STHs at 6 monthly intervals and sustained prompt malaria treatment significantly reduced the overall prevalence of S. haematobium, S. mansoni, hookworms and P. falciparum infection in primary schoolchildren by 73.5%, 70.8%, 67.3% and 58.8% respectively (p P. f + schistosomes, and P. f + STHs + schistosomes co-infections were reduced by 68.0%, 84.2%, and 90.7%, respectively. The absence of anti-helminthic treatment between the 12 mth and 33 mth follow-up surveys resulted in the sharp increase in STHs + schistosomes co-infection from 3.3% at 12 months follow up survey to 10.7%, slightly more than the baseline level (10.3% while other

Evaluation of morphological changes of the biliary tree by magnetic resonance cholangiography in patients with schistosomiasis mansoni: interobserver agreement

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Sales, Danilo Moulin; Leao, Alberto Ribeiro de Souza; Santos, Jose Eduardo Mourao dos; Shigueoka, David Carlos; Colleoni Neto, Ramiro [Universidade Federal de Sao Paulo (Unifesp/EPM), Sao Paulo, SP (Brazil)], e-mail: daniloevaleria@uol.com.br; Borges, Durval Rosa; D' Ippolito, Giuseppe; Szejnfeld, Jacob [Universidade Federal de Sao Paulo (Unifesp/EPM), Sao Paulo, SP (Brazil). Dept. of Medicine

2009-09-15

Objective: To describe changes of the biliary tree demonstrated by magnetic resonance cholangiography (MRC) in patients with the hepatosplenic presentation of schistosomiasis mansoni, and evaluating the interobserver agreement in the detection of schistosomal cholangiopathy. Results: prospective, cross-sectional study involving 24 patients with hepatosplenic schistosomiasis and 6 healthy patients (control group) submitted to biliary tree evaluation by MRC. The following changes of the biliary tree were considered: distortion, thinning, stenosis, dilation and irregularity. The interobserver agreement in the detection of biliary tree changes was calculated with the McNemar's test and the kappa index of agreement ({kappa}). Results: the interobserver agreement in the detection of distortion and thinning of the biliary tree was almost perfect ({kappa} = 0.867; confidence interval [CI] 95% [0.512-1.0] and {kappa} = 0.865; CI 95% [0.51-1.0], respectively). There was a substantial agreement for stenosis ({kappa} = 0.78; CI 95% [0.424-1.0]), moderate agreement for dilation ({kappa} = 0.595; CI 95% [0.247-0.942]) and mild agreement for thinning ({kappa} = 0.229; CI 95% [0.095-0.552]). Conclusion: in a decreasing order of frequency, the changes of the biliary tree were observed: distortion, thinning, stenosis, dilation and irregularity. The interobserver agreement for signs of schistosomal cholangiopathy was almost perfect for distortion and thinning, and substantial for stenosis. (author)

Implications of Changing Temperatures on the Growth, Fecundity and Survival of Intermediate Host Snails of Schistosomiasis: A Systematic Review

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Chester Kalinda

2017-01-01

Full Text Available Climate change has been predicted to increase the global mean temperature and to alter the ecological interactions among organisms. These changes may play critical roles in influencing the life history traits of the intermediate hosts (IHs. This review focused on studies and disease models that evaluate the potential effect of temperature rise on the ecology of IH snails and the development of parasites within them. The main focus was on IH snails of schistosome parasites that cause schistosomiasis in humans. A literature search was conducted on Google Scholar, EBSCOhost and PubMed databases using predefined medical subject heading terms, Boolean operators and truncation symbols in combinations with direct key words. The final synthesis included nineteen published articles. The studies reviewed indicated that temperature rise may alter the distribution, optimal conditions for breeding, growth and survival of IH snails which may eventually increase the spread and/or transmission of schistosomiasis. The literature also confirmed that the life history traits of IH snails and their interaction with the schistosome parasites are affected by temperature and hence a change in climate may have profound outcomes on the population size of snails, parasite density and disease epidemiology. We concluded that understanding the impact of temperature on the growth, fecundity and survival of IH snails may broaden the knowledge on the possible effects of climate change and hence inform schistosomiasis control programmes.

Technical report on the development of egg allergy vaccine using novel technology fused with radiation technology and biotechnology

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Byun, Myung Woo; Lee, Ju Woon; Kim, Jae Hun

2007-01-01

Type I allergy has become increasingly prevalent over the past few decades. Current immunotherapy for allergic disease is effective in the treatment of respiratory allergies by administration of natural allergen extracts. Injection of food allergen extract can bring on high rate of adverse systemic reaction. Such traditional injection immunotherapy for food allergy is currently not recommended because of the allergic side effects of the therapy. Therefore, effective preventive and therapeutic strategies for food allergy are urgently needed. Allergenicity of allergen by a treatment of radiation were decreased and irradiated allergen was showed immunological change in vivo. Here this study presents an approach for vaccination of irradiated allergen to prevent allergic response and the feasibility for allergy treatment by modified allergen. Gamma irradiation of OVA caused a reduced humoral and cellular immune responses specific to the allergen OVA in preventive and therapeutic effects, and its related mechanisms were associated with down-regulation of OVA-specific T cell activation in preventive effect. From adoptive cell transfer experiment results. T cell of spleen cells is critical role in the suppressive effect of humoral and cellular response on OVA-induced allergy

Mutual enhancement of IL-2 and IL-7 on DNA vaccine immunogenicity mainly involves regulations on their receptor expression and receptor-expressing lymphocyte generation.

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Zhang, Yonghong; Liang, Shuang; Li, Xiujin; Wang, Liyue; Zhang, Jianlou; Xu, Jian; Huo, Shanshan; Cao, Xuebin; Zhong, Zhenyu; Zhong, Fei

2015-07-09

Our previous study showed that IL-2 and IL-7 could mutually enhance the immunogenicity of canine parvovirus VP2 DNA vaccine, although the underlying mechanism remained unknown. Here, we used the OVA gene as a DNA vaccine in a mouse model to test their enhancement on DNA vaccine immunogenicity and to explore the molecular mechanism. Results showed that both IL-2 and IL-7 genes significantly increased the immunogenicity of OVA DNA vaccine in mice. Co-administration of IL-2 and IL-7 genes with OVA DNA significantly increased OVA-specific antibody titers, T cell proliferation and IFN-γ production compared with IL-2 or IL-7 alone, confirming that IL-2 and IL-7 mutually enhanced DNA vaccine immunogenicity. Mechanistically, we have shown that IL-2 significantly stimulated generation of IL-7 receptor-expressing lymphocytes, and that IL-7 significantly induced IL-2 receptor expression. These results contribute to an explanation of the mechanism of the mutual effects of IL-2 and IL-7 on enhancing DNA vaccine immunogenicity and provided a basis for further investigation on their mutual effects on adjuvant activity and immune regulation. Copyright © 2015 Elsevier Ltd. All rights reserved.

Technical report on the development of egg allergy vaccine using novel technology fused with radiation technology and biotechnology

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Byun, Myung Woo; Lee, Ju Woon; Kim, Jae Hun

2007-01-15

Type I allergy has become increasingly prevalent over the past few decades. Current immunotherapy for allergic disease is effective in the treatment of respiratory allergies by administration of natural allergen extracts. Injection of food allergen extract can bring on high rate of adverse systemic reaction. Such traditional injection immunotherapy for food allergy is currently not recommended because of the allergic side effects of the therapy. Therefore, effective preventive and therapeutic strategies for food allergy are urgently needed. Allergenicity of allergen by a treatment of radiation were decreased and irradiated allergen was showed immunological change in vivo. Here this study presents an approach for vaccination of irradiated allergen to prevent allergic response and the feasibility for allergy treatment by modified allergen. Gamma irradiation of OVA caused a reduced humoral and cellular immune responses specific to the allergen OVA in preventive and therapeutic effects, and its related mechanisms were associated with down-regulation of OVA-specific T cell activation in preventive effect. From adoptive cell transfer experiment results. T cell of spleen cells is critical role in the suppressive effect of humoral and cellular response on OVA-induced allergy.

A Novel Anti-Inflammatory Role for Ginkgolide B in Asthma via Inhibition of the ERK/MAPK Signaling Pathway

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Xiao Chu

2011-09-01

Full Text Available Ginkgolide B is an anti-inflammatory extract of Ginkgo biloba and has been used therapeutically. It is a known inhibitor of platelet activating factor (PAF, which is important in the pathogenesis of asthma. Here, a non-infectious mouse model of asthma is used to evaluate the anti-inflammatory capacity of ginkgolide B (GKB and characterize the interaction of GKB with the mitogen activated protein kinase (MAPK pathway. BALB/c mice that were sensitized and challenged to ovalbumin (OVA were treated with GKB (40 mg/kg one hour before they were challenged with OVA. Our study demonstrated that GKB may effectively inhibit the increase of T-helper 2 cytokines, such as interleukin (IL-5 and IL-13 in bronchoalveolar lavage fluid (BALF. Furthermore, the eosinophil count in BALF significantly decreased after treatment of GKB when compared with the OVA-challenged group. Histological studies demonstrated that GKB substantially inhibited OVA-induced eosinophilia in lung tissue and mucus hyper-secretion by goblet cells in the airway. These results suggest that ginkgolide B may be useful for the treatment of asthma and its efficacy is related to suppression of extracellular regulating kinase/MAPK pathway.

Suppressive effects of anti-allergic agent suplatast tosilate (IPD-1151T on the expression of co-stimulatory molecules on mouse splenocytes in vivo

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Masatsugu Kurokawa

2001-01-01

Full Text Available The effects of IPD-1151T on the expression of costimulatory molecules, CD40, CD80 and CD86, were investigated in vivo using mice with allergic disorders. BALB/c mice were immunized intraperitoneally with two doses of dinitrophenylated ovalbumin (DNP-OVA at 1-week intervals. These mice then were treated intraperitoneally with 100μg/kg of IPD1151T once a day for 14 days, starting 7 days after the first immunization. On day 21, some mice were challenged intraperitoneally with DNP-OVA and the other mice were not challenged. All mice were autopsied on day 22 and assayed for immunoglobulin E, interleuken (IL-4 and IL-5 productions following DNP-OVA immunization. The intraperitoneal treatment with IPD-1151T strongly suppressed immunoglobulin E contents in serum, which were enhanced by DNA-OVA immunization. IPD-1151T also caused a decrease in both IL-4 and IL-5 levels in splenic lymphocytes. We next examined the influence of IPD1151T on co-stimulatory molecule expression on splenic lymphocytes. IPD-1151T caused suppression of CD40 and CD86 expression; however, the treatments did not affect CD80 expression.

Immunopathological modifications in the rectal mucosa from an animal model of food allergy Modificaciones inmunopatológicas de la mucosa rectal en un modelo animal de alergia alimentaria

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M. Vinuesa

2005-09-01

Full Text Available Aim: the aim is to determine immunopathological modifications in rectal mucosa from rabbit after local challenge in sensitized animals with ovalbumin (OVA. Experimental design: thirty rabbits divided into three groups: G1: normal, G2: subcutaneously OVA sensitized, G3: sensitized, locally OVA challenged and sampled 4 hours after challenge. Specific anti-OVA IgE levels were evaluated by passive cutaneous anaphylaxis test (PCA. In each group 200 high microscopical power fields (HPF were counted. Results were expressed as arithmetic mean and SE. Statistical analysis was made using Student t test. Anti-CD4, CD5, µ chain, CD25 and RLA II monoclonal antibodies were used. Avidin biotin horseradish peroxidase system was used. Results: CD 4: G1: 8,3 ± 0,06; G2: 13,4 ± 0,08 and G3: 8,25 ± 0,06. CD 5: G1: 7,3 ± 0,05; G2: 9,4 ± 0,05 and G3: 11,3 ± 0,06. CD 25: G1: 13 ± 0,08; G2: 15,1 ± 0,13 and G3: 25,5 ± 0,15. m chain: G1: 10,4 ± 0,06; G2: 3,8 ± 0,02 and G3: 6,0 ± 0,10. RLA II (DR: G1: 11,6 ± 0,O5; G2: 19,2 ± 0,09 and G3: 19,1 ± 0,11. In all cases, experimental groups (G2 and G3 presented statistical significant differences vs. control group (G1 (p Objetivo: determinar las modificaciones inmunopatológicas en la mucosa rectal de conejo sensibilizado con ovoalbúmina (OVA y desafiado localmente. Diseño experimental: treinta conejos divididos en tres grupos G1: normal; G2 sensibilizado por vía subcutánea con OVA y G3: sensibilizado y desafiado localmente con OVA y muestreados 4 horas después del desafío. Los niveles de IgE anti-OVA específica fueron evaluados por el test de anafilaxia cutánea pasiva (PCA. Se contaron 200 campos de mayor aumento en cada grupo. Los resultados fueron expresados como media aritmética y error standard aplicándose el test de la t de Student. Resultados: CD 4: G1: 8,3 ± 0,06; G2: 13,4 ± 0,08 y G3: 8,25 ± 0,06. CD 5: G1: 7,3 ± 0,05; G2: 9,4 ± 0,05 y G3: 11,3 ± 0,06. CD 25: G1: 13., ± 0,08; G2: 15,1 �

Drug discovery for schistosomiasis: hit and lead compounds identified in a library of known drugs by medium-throughput phenotypic screening.

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Maha-Hamadien Abdulla

2009-07-01

Full Text Available Praziquantel (PZQ is the only widely available drug to treat schistosomiasis. Given the potential for drug resistance, it is prudent to search for novel therapeutics. Identification of anti-schistosomal chemicals has traditionally relied on phenotypic (whole organism screening with adult worms in vitro and/or animal models of disease-tools that limit automation and throughput with modern microtiter plate-formatted compound libraries.A partially automated, three-component phenotypic screen workflow is presented that utilizes at its apex the schistosomular stage of the parasite adapted to a 96-well plate format with a throughput of 640 compounds per month. Hits that arise are subsequently screened in vitro against adult parasites and finally for efficacy in a murine model of disease. Two GO/NO GO criteria filters in the workflow prioritize hit compounds for tests in the animal disease model in accordance with a target drug profile that demands short-course oral therapy. The screen workflow was inaugurated with 2,160 chemically diverse natural and synthetic compounds, of which 821 are drugs already approved for human use. This affords a unique starting point to 'reposition' (re-profile drugs as anti-schistosomals with potential savings in development timelines and costs.Multiple and dynamic phenotypes could be categorized for schistosomula and adults in vitro, and a diverse set of 'hit' drugs and chemistries were identified, including anti-schistosomals, anthelmintics, antibiotics, and neuromodulators. Of those hits prioritized for tests in the animal disease model, a number of leads were identified, one of which compares reasonably well with PZQ in significantly decreasing worm and egg burdens, and disease-associated pathology. Data arising from the three components of the screen are posted online as a community resource.To accelerate the identification of novel anti-schistosomals, we have developed a partially automated screen workflow that

Urinary estrogen metabolites and self-reported infertility in women infected with Schistosoma haematobium.

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Júlio Santos

Full Text Available BACKGROUND: Schistosomiasis is a neglected tropical disease, endemic in 76 countries, that afflicts more than 240 million people. The impact of schistosomiasis on infertility may be underestimated according to recent literature. Extracts of Schistosoma haematobium include estrogen-like metabolites termed catechol-estrogens that down regulate estrogen receptors alpha and beta in estrogen responsive cells. In addition, schistosome derived catechol-estrogens induce genotoxicity that result in estrogen-DNA adducts. These catechol estrogens and the catechol-estrogen-DNA adducts can be isolated from sera of people infected with S. haematobium. The aim of this study was to study infertility in females infected with S. haematobium and its association with the presence of schistosome-derived catechol-estrogens. METHODOLOGY/PRINCIPAL FINDINGS: A cross-sectional study was undertaken of female residents of a region in Bengo province, Angola, endemic for schistosomiasis haematobia. Ninety-three women and girls, aged from two (parents interviewed to 94 years were interviewed on present and previous urinary, urogenital and gynecological symptoms and complaints. Urine was collected from the participants for egg-based parasitological assessment of schistosome infection, and for liquid chromatography diode array detection electron spray ionization mass spectrometry (LC/UV-DAD/ESI-MSn to investigate estrogen metabolites in the urine. Novel estrogen-like metabolites, potentially of schistosome origin, were detected in the urine of participants who were positive for eggs of S. haematobium, but not detected in urines negative for S. haematobium eggs. The catechol-estrogens/ DNA adducts were significantly associated with schistosomiasis (OR 3.35; 95% CI 2.32-4.84; P≤0.001. In addition, presence of these metabolites was positively associated with infertility (OR 4.33; 95% CI 1.13-16.70; P≤0.05. CONCLUSIONS/SIGNIFICANCE: Estrogen metabolites occur widely in diverse

Activation of Antigen-Specific CD8(+) T Cells by Poly-DL-Lactide/Glycolide (PLGA) Nanoparticle-Primed Gr-1(high) Cells.

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Luo, Wen-Hui; Yang, Ya-Wun

2016-04-01

The aim of this study was to investigate the induction of antigen-specific T cell activation and cell cycle modulation by a poly-DL-lactide/glycolide (PLGA) nanoparticle (NP)-primed CD11b(+)Gr-1(high) subset isolated from mouse bone marrow. PLGA NPs containing the ovalbumin (OVA) antigen were prepared using the double emulsion and solvent evaporation method, and protein release rate and cell viability were determined. The Lin2(¯)CD11b(+)Gr-1(high)Ly6c(low) (Gr-1(high)) subset was sorted from the bone marrow of C57BL/6 J mice by fluorescence-activated cell sorting (FACS) and co-cultured with OT-I CD8(+) splenic T cells. Proliferation of OT-I CD8(+) T cells was monitored, and cell cycles were determined by 5-bromo-2'-deoxyuridine (BrdU) labeling. Treatment of Gr-1(high) cells with PLGA/OVA NPs upregulated expression of the SIINFEKL-H2K(b) complex in the context of MHC I. Co-cultures of OT-I CD8(+) T cells with the PLGA/OVA NP-primed Gr-1(high) cells induced the proliferation of T cells in vitro and modulated cell division and morphology. Treatment of Gr-1(high) cells with PLGA/OVA NPs also induced cell apoptosis and necrosis. This study demonstrated the function of PLGA/OVA NPs in the activation of OT-I CD8(+) T cells and the capability of cross-presentation via the Gr-1(high) polymorphonuclear subset from mouse bone marrow.

Postincident Support for Healthcare Workers Experiencing Occupational Violence and Aggression.

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Shea, Tracey; Cooper, Brian; De Cieri, Helen; Sheehan, Cathy; Donohue, Ross; Lindsay, Sarah

2018-05-10

To investigate the relative contributions of workplace type, occupational violence and aggression (OVA) strategies and interventions along with perceptions of the occupational health and safety (OHS) environment on the likelihood of receiving postincident support following the experience of OVA. We used a cross-sectional study design with an online survey to collect data from employees in nursing and midwifery in Victoria, Australia. Survey data collected from 3,072 members of the Australian Nursing and Midwifery Federation (Victorian branch) were analyzed using logistic regression. Of the 3,072 respondents who had experienced OVA in the preceding 12 months, 1,287 (42%) reported that they had received postincident support. Hierarchical logistic regression revealed that the OHS environment was the dominant factor that predicted the likelihood of workers receiving postincident support. Working in a positive OHS environment characterized by higher levels of leading indicators of OHS, prioritization of OHS, supervisor support for safety, and team psychological safety was the stronger predictor of postincident support. Being employed in a workplace that offered training in the management and prevention of OVA also increased the likelihood of receiving postincident support. While training in the management and prevention of OVA contributed to the likelihood of receiving postincident support, a greater emphasis on the OHS environment was more important in predicting the likelihood that workers received support. This study identifies workplace practices that facilitate the provision of postincident support for healthcare workers. Facilitating effective postincident support could improve outcomes for workers, their patients and workplaces, and society in general. © 2018 Sigma Theta Tau International.

Protective effects of Scrophularia striata in Ovalbumin-induced mice asthma model

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2013-01-01

Background Scrophularia striata Boiss. (Scrophulariaceae) is a plant growing in the northeastern part of Iran and being used as a traditional herb for various inflammatory disorders. This study was designed to investigate the protective effects of the Scrophularia striata extract in Ovalbumin (OVA) induced-asthma mice model. Methods OVA-sensitized mice were intrapritonealy treated with two doses (100 and 200 mg/kg) of the extract on days 8 to 14 separately. Broncoalveolar lavage fluids (BALF) was collected 48 h after the final OVA challenge and then the number of eosinophils and other inflammatory cells were assessed by direct microscopic counting. In addition, total immunoglubolin (Ig) E and OVA-specific IgE levels in serum, IL-4 and IL-5 cytokines in BALF were determined by Enzyme-Linked Immunosorbent Assay. Moreover, phytochemical assay by thin layer chromatography (TLC) and the 2, 2 diphenyl-1-picrylhydrazyl (DPPH) were used to evaluate the main compounds and the antioxidant capacity of the plant extract, respectively. Results The results showed that the main components; including flavonoids, phenolic compounds and phenyl propanoids were presented in the S. striata extract. In addition, the treatment with extract significantly reduced the number of inflammatory cells and suppressed T-helper 2 (Th2) cytokines including IL-4 and IL-5 in BALF. Also, total IgE and OVA-specific IgE levels in the serum decreased. Conclusion Collectively, it is concluded that the extract has the potential to modulate the Th2 cytokines and could be used as immunomodulatory agent in the treatment of allergic asthma. PMID:23837463

Protein-coated nanoparticles are internalized by the epithelial cells of the female reproductive tract and induce systemic and mucosal immune responses.

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Savannah E Howe

Full Text Available The female reproductive tract (FRT includes the oviducts (fallopian tubes, uterus, cervix and vagina. A layer of columnar epithelium separates the endocervix and uterus from the outside environment, while the vagina is lined with stratified squamous epithelium. The mucosa of the FRT is exposed to antigens originating from microflora, and occasionally from infectious microorganisms. Whether epithelial cells (ECs of the FRT take up (sample the lumen antigens is not known. To address this question, we examined the uptake of 20-40 nm nanoparticles (NPs applied vaginally to mice which were not treated with hormones, epithelial disruptors, or adjuvants. We found that 20 and 40 nm NPs are quickly internalized by ECs of the upper FRT and within one hour could be observed in the lymphatic ducts that drain the FRT, as well as in the ileac lymph nodes (ILNs and the mesenteric lymph nodes (MLNs. Chicken ovalbumin (Ova conjugated to 20 nm NPs (NP-Ova when administered vaginally reaches the internal milieu in an immunologically relevant form; thus vaginal immunization of mice with NP-Ova induces systemic IgG to Ova antigen. Most importantly, vaginal immunization primes the intestinal mucosa for secretion of sIgA. Sub-cutaneous (s.c boosting immunization with Ova in complete Freund's adjuvant (CFA further elevates the systemic (IgG1 and IgG2c as well as mucosal (IgG1 and sIgA antibody titers. These findings suggest that the modes of antigen uptake at mucosal surfaces and pathways of antigen transport are more complex than previously appreciated.

The Metalloporphyrin Antioxidant, MnTE-2-PyP, Inhibits Th2 Cell Immune Responses in an Asthma Model

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Paiboon Jungsuwadee

2012-08-01

Full Text Available MnTE-2-PyP, a superoxide dismutase mimetic, inhibited OVA-induced airway inflammation in mice suggesting an effect on Th2 responsiveness. Thus, we hypothesized that MnTE-2-PyP may alter dendritic cell-Th2 interactions. Bone marrow derived dendritic cells (DC and OVA_323-339-specific Th2 cells were cultured separately in the presence or absence of MnTE-2-PyP for 3 days prior to the co-culturing of the two cell types in the presence of an OVA_323-339 peptide and in some cases stimulated with CD3/CD28. MnTE-2-PyP-pretreated DC inhibited IL-4, IL-5 and IFNγ production and inhibited Th2 cell proliferation in the DC-Th2 co-culturing system in the presence of the OVA_323-339 peptide. Similar results were obtained using the CD3/CD28 cell-activation system; the addition of MnTE-2-PyP inhibited Th2 cell proliferation. MnTE-2-PyP suppressed CD25 expression on OVA-specific Th2 cells, which implied that MnTE-2-PyP can inhibit the activation of Th2 cells. MnTE-2-PyP also down-regulated co-stimulatory molecules: CD40, CD80 and CD86 on immature DC. Our studies suggest that the major mechanism by which MnTE-2-PyP inhibits airway inflammation is by acting on the DC and suppressing Th2 cell proliferation and activation.

House dust extracts have both TH2 adjuvant and tolerogenic activities.

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Ng, Nicholas; Lam, Diane; Paulus, Petra; Batzer, Glenda; Horner, Anthony A

2006-05-01

Although mechanisms remain a subject of controversy, there is general agreement that living environments influence allergic risk during the first years of life. We reasoned that sterile house dust extracts (HDEs) would have immunologic activities reflective of their environments of origin and therefore would be useful surrogates for investigations of how ambient exposures influence immune homeostasis. These experiments determined how airway HDE exposures influence adaptive responses to a coadministered antigen and subsequent airway hypersensitivity responses to antigen challenge. Mice received intranasal ovalbumin (OVA) vaccinations on a weekly basis. Select groups of mice also received intranasal HDE weekly with OVA; daily at one seventh the weekly dose, beginning 7 days before the first OVA sensitization; or both. Weekly intranasal vaccinations with OVA and HDE primed mice for the development of T(H)2-biased immune and airway hypersensitivity responses. In contrast, daily low-dose intranasal HDE exposures protected against the immunologic and pathologic outcomes associated with weekly intranasal OVA/HDE vaccinations. The T(H)2 adjuvant activities of HDEs were found to be dependant on MyD88, a molecule critical for signaling through a majority of Toll-like receptors. Moreover, the tolerogenic activity associated with daily intranasal HDE exposures could be replicated with LPS. These investigations demonstrate that in addition to allergens, living environments contain immunomodulatory materials with both T(H)2 adjuvant and tolerogenic activities. As the contents of HDEs are ubiquitous, these experiments might recapitulate and help explain clinically relevant immunologic events involved in the maintenance of aeroallergen tolerance and the dysregulated responses that lead to allergic respiratory diseases.

An extract of Crataegus pinnatifida fruit attenuates airway inflammation by modulation of matrix metalloproteinase-9 in ovalbumin induced asthma.

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In Sik Shin

Full Text Available BACKGROUND: Crataegus pinnatifida (Chinese hawthorn has long been used as a herbal medicine in Asia and Europe. It has been used for the treatment of various cardiovascular diseases such as myocardial weakness, tachycardia, hypertension and arteriosclerosis. In this study, we investigated the anti-inflammatory effects of Crataegus pinnatifida ethanolic extracts (CPEE on Th2-type cytokines, eosinophil infiltration, expression of matrix metalloproteinase (MMP-9, and other factors, using an ovalbumin (OVA-induced murine asthma model. METHODS/PRINCIPAL FINDING: Airways of OVA-sensitized mice exposed to OVA challenge developed eosinophilia, mucus hypersecretion and increased cytokine levels. CPEE was applied 1 h prior to OVA challenge. Mice were administered CPEE orally at doses of 100 and 200 mg/kg once daily on days 18-23. Bronchoalveolar lavage fluid (BALF was collected 48 h after the final OVA challenge. Levels of interleukin (IL-4 and IL-5 in BALF were measured using enzyme-linked immunosorbent (ELISA assays. Lung tissue sections 4 µm in thickness were stained with Mayer's hematoxylin and eosin for assessment of cell infiltration and mucus production with PAS staining, in conjunction with ELISA, and Western blot analyses for the expression of MMP-9, intercellular adhesion molecule (ICAM-1 and vascular cell adhesion molecule (VCAM-1 protein expression. CPEE significantly decreased the Th2 cytokines including IL-4 and IL-5 levels, reduced the number of inflammatory cells in BALF and airway hyperresponsiveness, suppressed the infiltration of eosinophil-rich inflammatory cells and mucus hypersecretion and reduced the expression of ICAM-1, VCAM-1 and MMP-9 and the activity of MMP-9 in lung tissue of OVA-challenged mice. CONCLUSIONS: These results showed that CPEE can protect against allergic airway inflammation and can act as an MMP-9 modulator to induce a reduction in ICAM-1 and VCAM-1 expression. In conclusion, we strongly suggest the feasibility

First detection of Allobilharzia visceralis (Schistosomatidae, Trematoda) from Cygnus cygnus in Japan.

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Hayashi, Kei; Ichikawa-Seki, Madoka; Ohari, Yuma; Mohanta, Uday Kumar; Aita, Junya; Satoh, Hiroshi; Ehara, Shiori; Tokashiki, Minami; Shiroma, Tomoko; Azuta, Ayumi; Oka, Nozomi; Watanabe, Takuya; Harasawa, Ryo; Inohana, Satoshi; Ichijo, Toshihiro; Furuhama, Kazuhisa

2017-02-01

Adult schistosomes were detected in the veins or capillaries of the large intestine, mesentery, liver, and adrenal glands in eight of 13 whooper swans (Cygnus cygnus) examined in Iwate Prefecture, Japan. However, neither eggs nor severe tissue injuries were observed in any of the swans. The schistosomes were definitively identified as Allobilharzia visceralis based on the nucleotide sequences of the ribosomal internal transcribed spacer (ITS) region. Allobilharzia visceralis infections have been reported in whooper swan in Iceland and tundra swan (Cygnus columbianus) in North America. These detections suggest that A. visceralis is distributed extensively along the swan flyways because the swans are migratory birds. To the best of our knowledge, this is the first report of A. visceralis infection in Asia. Copyright © 2016. Published by Elsevier Ireland Ltd.

Acrolein exposure suppresses antigen-induced pulmonary inflammation

Science.gov (United States)

2013-01-01

Background Adverse health effects of tobacco smoke arise partly from its influence on innate and adaptive immune responses, leading to impaired innate immunity and host defense. The impact of smoking on allergic asthma remains unclear, with various reports demonstrating that cigarette smoke enhances asthma development but can also suppress allergic airway inflammation. Based on our previous findings that immunosuppressive effects of smoking may be largely attributed to one of its main reactive electrophiles, acrolein, we explored the impact of acrolein exposure in a mouse model of ovalbumin (OVA)-induced allergic asthma. Methods C57BL/6 mice were sensitized to ovalbumin (OVA) by intraperitoneal injection with the adjuvant aluminum hydroxide on days 0 and 7, and challenged with aerosolized OVA on days 14–16. In some cases, mice were also exposed to 5 ppm acrolein vapor for 6 hrs/day on days 14–17. Lung tissues or brochoalveolar lavage fluids (BALF) were collected either 6 hrs after a single initial OVA challenge and/or acrolein exposure on day 14 or 48 hrs after the last OVA challenge, on day 18. Inflammatory cells and Th1/Th2 cytokine levels were measured in BALF, and lung tissue samples were collected for analysis of mucus and Th1/Th2 cytokine expression, determination of protein alkylation, cellular thiol status and transcription factor activity. Results Exposure to acrolein following OVA challenge of OVA-sensitized mice resulted in markedly attenuated allergic airway inflammation, demonstrated by decreased inflammatory cell infiltrates, mucus hyperplasia and Th2 cytokines. Acrolein exposure rapidly depleted lung tissue glutathione (GSH) levels, and induced activation of the Nrf2 pathway, indicated by accumulation of Nrf2, increased alkylation of Keap1, and induction of Nrf2-target genes such as HO-1. Additionally, analysis of inflammatory signaling pathways showed suppressed activation of NF-κB and marginally reduced activation of JNK in acrolein

Intestinal helminthiasis in children with chronic neurological disorders in Benin City, Nigeria: intensity and behavioral risk factors.

Science.gov (United States)

Nwaneri, Damia Uchechukwu; Ibadin, Michael Okoeguale; Ofovwe, Gabriel Egberue; Sadoh, Ayebo Evawere

2013-05-01

Behavioral aberrations such as nail biting, finger sucking, and pica have been postulated as risk factors that enhance helminths ova transmission. These aberrations may present commonly in children with chronic neurological disorders and predispose them to heavy intensity of intestinal helminthiasis. This comparative cross-sectional study was to determine the prevalence, intensity, and behavioral risk factors for intestinal helminthiasis in children with chronic neurological disorders and apparently healthy controls. Fresh stool samples from 155 children (2-17 years) with chronic neurological disorders seen at the child neurology clinic and 155 age and sex matched controls from nursery and primary schools in Benin City were analyzed using the Kato-Katz technique for detection of ova of helminths from November 2008 to April 2009. The prevalence of intestinal helminthiasis (31.0%) was significantly higher in children with chronic neurological disorders compared with the controls (19.4%) (P=0.03). The intensity of infections in both groups was light ranging 24-144 eggs per gram. Ascaris lumbricoides, Trichuris trichiura and hookworm were the intestinal helminths isolated in both groups. Behavioral aberrations were significantly more represented in the subjects than in the controls (Phelminthiasis (P=0.025 and 0.001, respectively) in the subjects only. Hand washing with water and soap after defecation and frequent de-worming exercise were practices significantly associated with decreased prevalence of intestinal helminthiasis in the subjects and controls. Behavioral modification in children with chronic neurological disorders should be an integral part of the control program for intestinal helminthiasis.

Comparison of the changes of the antigenicities of a hen's egg albumin by a gamma and an electron beam irradiation

International Nuclear Information System (INIS)

Lee, Ju-Woon; Seo, Ji-Hyun; Kim, Jae-Hun; Lee, Soo-Young; Byun, Myung-Woo

2007-01-01

The study was conducted to compare the radiation types of a gamma ray and an electron beam for the inhibition and reduction of a food allergy. OVA (2 mg/ml) were irradiated at 3, 5, 7 and 10 kGy. Patterns detected by the SDS-PAGE and an immunoblot showed that the intact OVA band disappeared and that it was dependant upon the radiation doses regardless of the radiation types. Binding abilities of the irradiated OVA against the monoclonal IgG and the egg allergic patients' IgE decreased due to a conformational change of the epitope, but differences from using the two different radiation types were not observed. The results indicate that both the radiation types can be used for an inhibition and a reduction of a food allergy regardless of the radiation types

Association of urogenital symptoms with history of water contact in young women in areas endemic for S. haematobium

DEFF Research Database (Denmark)

Galappaththi-Arachchige, Hashini Nilushika; Hegertun, Ingrid Elise Amlie; Holmen, Sigve

2016-01-01

schistosomiasis. In a cross-sectional study in rural South Africa, 883 sexually active women aged 16–22 years were included. Questions were asked about urogenital symptoms and water contact history. Urine samples were tested for S. haematobium ova. A score based on self-reported water contact was calculated......Female genital schistosomiasis is a neglected tropical disease caused by Schistosoma haematobium. Infected females may suffer from symptoms mimicking sexually transmitted infections. We explored if self-reported history of unsafe water contact could be used as a simple predictor of genital...... and the association with symptoms was explored while adjusting for other genital infections using multivariable logistic regression analyses. S. haematobium ova were detected in the urine of 30.5% of subjects. Having ova in the urine was associated with the water contact score (p

Maximizing Tumor Immunity With Fractionated Radiation

International Nuclear Information System (INIS)

Schaue, Dörthe; Ratikan, Josephine A.; Iwamoto, Keisuke S.; McBride, William H.

2012-01-01

Purpose: Technologic advances have led to increased clinical use of higher-sized fractions of radiation dose and higher total doses. How these modify the pathways involved in tumor cell death, normal tissue response, and signaling to the immune system has been inadequately explored. Here we ask how radiation dose and fraction size affect antitumor immunity, the suppression thereof, and how this might relate to tumor control. Methods and Materials: Mice bearing B16-OVA murine melanoma were treated with up to 15 Gy radiation given in various-size fractions, and tumor growth followed. The tumor-specific immune response in the spleen was assessed by interferon-γ enzyme-linked immunospot (ELISPOT) assay with ovalbumin (OVA) as the surrogate tumor antigen and the contribution of regulatory T cells (Tregs) determined by the proportion of CD4 + CD25 hi Foxp3 + T cells. Results: After single doses, tumor control increased with the size of radiation dose, as did the number of tumor-reactive T cells. This was offset at the highest dose by an increase in Treg representation. Fractionated treatment with medium-size radiation doses of 7.5 Gy/fraction gave the best tumor control and tumor immunity while maintaining low Treg numbers. Conclusions: Radiation can be an immune adjuvant, but the response varies with the size of dose per fraction. The ultimate challenge is to optimally integrate cancer immunotherapy into radiation therapy.

Prevalence of schistosome induced cercarial dermatitis in north of Iran

Directory of Open Access Journals (Sweden)

Seif Ali Mahdavi

2013-02-01

Full Text Available Objective: To investigate the level of people’s infection to cecarial dermatitis in Mazandaran Province(north of Iran, where is susceptible to this disease due to Mazandaran’s climate. Methods: The present descriptive study is a cross sectional one and was done during 2010-2011. The sample and population were 2 310 people, randomly chosen in 77 clusters from 4 towns, 30 people in each cluster on average. The survey form was given to people house-by-house and the clinical observation of the positive cases were recorded. The related medicine (calamin ointment prevention methods were prescribed by the doctors of the research team and freely given to the infected patients. SPSS was applied to analyze the groups of age, sex, job and the part of the body infected. Results: Among the 2 310 population studied, 139 of them (6.1% were infected to cecarial dermatitis. Among the 139 people who had cecarial dermatitis, there was a significant difference in the amounts related to the groups of job, age and the part of body infected. Farmers were infected to this disease more than other vocations 74 (53.2%; people between 40-49 years were infected to cecarial dermatitis more than other age groups 38 (27.3%; leg was the most vulnerable bodypart 112 (80.6%. Conclusions: It can be concluded that since this farmers and 40-49 years group are more exposed to mud and dirty water, these people are more infected to cecarial dermatitis. Close cooperation among health and environment authorities should be carried out 40-49 years, to control this disease 40-49 years.

Defective Priming of CD4+ T Cell Responses During Pre-patent Schistosome Infection

Science.gov (United States)

2011-11-26

maculopapular rash [11]. Symptoms of acute infection are usually not seen in residents of endemic areas, likely because of desensitization developed in...secreting proteolytic enzymes and enter the circulation after a few days [11]. They migrate through the capillaries of the lung and after approximately...highlighting the potential for resistance [34]. However, there are limitations to chemotherapeutic control, including the expense of the drug itself

Similar cellular responses after treatment with either praziquantel or ...

African Journals Online (AJOL)

and age before being randomly allocated to one treatment, with either ..... Cioli D, Pica-Mattoccia L, Archer S. Antischistosomal drugs: past, present ... and .... approach to schistosome population dynamics and estimation of the life-span of ...

The effect of a therapeutic dendritic cell-based cancer vaccination depends on the blockage of CTLA-4 signaling

DEFF Research Database (Denmark)

Met, Ozcan; Wang, Mingjun; Pedersen, Anders E

2006-01-01

tumor cells, and later on these mice even rejected wild-type EL-4 tumor cells indicating that tumor epitope spreading takes place during the process of vaccination-induced E.G7-OVA rejection. In agreement with these observations, mice having rejected E.G7-OVA tumors showed long lasting CTL memory...... in spleen and bone marrow towards both the SIINFEKL-peptide and other EL-4-derived tumor rejecting epitopes....

Inhibitory effects of inhaled complex traditional Chinese medicine on early and late asthmatic responses induced by ovalbumin in sensitized guinea pigs

Directory of Open Access Journals (Sweden)

Gong Cheng-Chung

2011-09-01

Full Text Available Abstract Background Many formulae of traditional Chinese medicines (TCMs have been used for antiasthma treatment dating back many centuries. There is evidence to suggest that TCMs are effective as a cure for this allergenic disease administered via gastric tubes in animal studies; however, their efficacy, safety and side effects as an asthmatic therapy are still unclear. Methods In this study, guinea pigs sensitized with ovalbumin (OVA were used as an animal model for asthma challenge, and the sensitization of animals by bronchial reactivity to methacholine (Mch and the IgE concentration in the serum after OVA challenge were estimated. Complex traditional Chinese herbs (CTCM were administered to the animals by nebulization, and the leukocytes were evaluated from bronchoalveolar lavage fluid (BALF. Results The results showed that inhalation of CTCM could abolish the increased lung resistance (13-fold increase induced by challenge with OVA in the early asthmatic response (EAR, reducing to as low as baseline (1-fold. Moreover, our results indicated higher IgE levels (range, 78-83 ng/ml in the serum of sensitized guinea pigs than in the unsensitized controls (0.9 ± 0.256 ng/ml. In addition, increased total leukocytes and higher levels of eosinophils and neutrophils were seen 6 hours after challenge, and the increased inflammatory cells were reduced by treatment with CTCM inhalation. The interleukin-5 (IL-5 level in BALF was also reduced by CTCM. Conclusion Our findings indicate a novel method of administering traditional Chinese medicines for asthma treatment in an animal model that may be more effective than traditional methods.

Effects of Stingless Bee Propolis on Experimental Asthma

Directory of Open Access Journals (Sweden)

José Hidelbland Cavalcante de Farias

2014-01-01

Full Text Available Bee products have been used empirically for centuries, especially for the treatment of respiratory diseases. The present study evaluated the effect of treatment with a propolis hydroalcoholic extract (PHE produced by Scaptotrigona aff. postica stingless bee in a murine asthma model. BALB/c mice were immunized twice with ovalbumin (OVA subcutaneously. After 14 days, they were intranasally challenged with OVA. Groups P50 and P200 received PHE by gavage at doses of 50 and 200 mg/kg, respectively. The DEXA group was treated with intraperitoneal injection of dexamethasone. The OVA group received only water. The mice were treated daily for two weeks and then they were immunized a second time with intranasal OVA. The treatment with PHE decreased the cell number in the bronchoalveolar fluid (BAL. Histological analysis showed reduced peribronchovascular inflammation after treatment with PHE especially the infiltration of polymorphonuclear cells. In addition, the concentration of interferon-γ (IFN-γ in the serum was decreased. These results were similar to those obtained with dexamethasone. Treatment with S. aff postica propolis reduced the pathology associated with murine asthma due an inhibition of inflammatory cells migration to the alveolar space and the systemic progression of the allergic inflammation.

Effect of Kuwanon G isolated from the root bark of Morus alba on ovalbumin-induced allergic response in a mouse model of asthma.

Science.gov (United States)

Jung, Hyo Won; Kang, Seok Yong; Kang, Jong Seong; Kim, A Ryun; Woo, Eun-Rhan; Park, Yong-Ki

2014-11-01

The root bark of Morus alba L. (Mori Cortex Radicis; MCR) is traditionally used in Korean medicine for upper respiratory diseases. In this study, we investigated the antiasthmatic effect of kuwanon G isolated from MCR on ovalbumin (OVA)-induced allergic asthma in mice. Kuwanon G (1 and 10 mg/kg) was administered orally in mice once a day for 7 days during OVA airway challenge. We measured the levels of OVA-specific IgE and Th2 cytokines (IL-4, IL-5, and IL-13) in the sera or bronchoalveolar lavage (BAL) fluids and also counted the immune cells in BAL fluids. Histopathological changes in the lung tissues were analyzed. Kuwanon G significantly decreased the levels of OVA-specific IgE and IL-4, IL-5, and IL-13 in the sera and BAL fluids of asthma mice. Kuwanon G reduced the numbers of inflammatory cells in the BAL fluids of asthma mice. Furthermore, the pathological feature of lungs including infiltration of inflammatory cells, thickened epithelium of bronchioles, mucus, and collagen accumulation was inhibited by kuwanon G. These results indicate that kuwanon G prevents the pathological progression of allergic asthma through the inhibition of lung destruction by inflammation and immune stimulation. Copyright © 2014 John Wiley & Sons, Ltd.

Entrapment of ovalbumin into liposomes--factors affecting entrapment efficiency, liposome size, and zeta potential.

Science.gov (United States)

Brgles, Marija; Jurasin, Darija; Sikirić, Maja Dutour; Frkanec, Ruza; Tomasić, Jelka

2008-01-01

Various amounts of Ovalbumin (OVA) were encapsulated into positively and negatively charged multilamellar liposomes, with the aim to investigate the entrapment efficiency in different buffers and to study their effects on the liposome size and zeta potential. Results showed that the entrapment efficiency of OVA in anionic liposomes was the same in 10 mM Phosphate Buffer (PB) as in Phosphate-Buffered Saline (PBS; PB + 0.15 M NaCl). Also, liposome size was approximately 1200 nm for all anionic liposomes incorporating OVA. The entrapment efficiency of OVA in cationic liposomes was highly dependent on ionic strength. The size of cationic liposomes was approximately 1200 nm in PBS, regardless of protein content, but increased with the amount of the incorporated protein in PB. Aggregation of cationic liposomes in PB was observed when the mass of the protein was 2.5 mg or greater. The zeta potential of anionic liposomes was negative and of cationic liposomes positive in the whole range of protein mass tested. These results show how different compositions of lipid and aqueous phases can be used to vary the entrapment efficiency, liposome size, and zeta potential--the factors that are of great importance for the use of liposomes as drug carriers.

Hyaluronidase and hyaluronan in insect venom allergy.

Science.gov (United States)

King, Te Piao; Wittkowski, Knut M

2011-01-01

Insect venoms contain an allergen hyaluronidase that catalyzes the hydrolysis of hyaluronan (HA), a polymer of disaccharide GlcUA-GlcNAc in skin. HAs depending on their size have variable function in inflammation and immunity. This paper reports on whether hyaluronidase, HA polymers and oligomers can promote antibody response in mice. HA oligomers (8- to 50-mer; 3-20 kDa) were obtained by bee venom hyaluronidase digestion of HA polymers (750- to 5,000-mer; 300-2,000 kDa). Antibody responses in mice were compared following 3 biweekly subcutaneous injection of ovalbumin (OVA) with or without test adjuvant. OVA-specific IgG1 levels were approximately 2 times higher in BALB/c and C3H/HeJ mice receiving OVA and HA oligomer or polymer than those treated with OVA alone, and no increase in total IgE level was observed. In C57Bl/6 mice, observed increases in IgG1 and IgE were 3.5- and 1.7-fold, respectively, for the oligomer and 16- and 5-fold (p Insect venoms also have cytolytic peptides and phospholipases with inflammatory roles. These activities found in mice may contribute to venom allergenicity in susceptible people. Copyright © 2011 S. Karger AG, Basel.

Law No. 353, 3 June 1987.

Science.gov (United States)

1987-01-01

This document summarizes Denmark's 1987 Law establishing an Ethical Council regulating health care services and biomedical research on human subjects. The work of the Council will be based on the assumption that human life begins at fertilization. The Council will recommend laws to protect fertilized human ova, living embryos, and fetuses. The Council will also make recommendations about: 1) the right to perform gene therapy on human gametes or fertilized human ova, embryos, and fetuses; 2) the right to use new diagnostic techniques to detect congenital defeats or diseases in fertilized human ova, embryos, and fetuses; and 3) the establishment of rules on deep freezing of human gametes and fertilized human ova. In addition, the Council will advise the scientific ethical committees on general ethical matters concerning experiments on human volunteers; advise health authorities on general ethical questions associated with new treatments, diagnostic techniques, and medical technology; and advise public authorities on matters relating to registration, release, and use of information on hereditary diseases. The Law prohibits experiments enabling the production of genetically identical human beings, those enabling the production of human beings by the fusion of genetically different embryos or parts of embryos prior to implantation, and those seeking to produce hybrids of human beings and other species.

A sub-population of circulating porcine gammadelta T cells can act as professional antigen presenting cells.

Science.gov (United States)

Takamatsu, H-H; Denyer, M S; Wileman, T E

2002-09-10

A sub-population of circulating porcine gammadelta T cells express cell surface antigens associated with antigen presenting cells (APCs), and are able to take up soluble antigen very effectively. Functional antigen presentation by gammadelta T cells to memory helper T cells was studied by inbred pig lymphocytes immunised with ovalbumin (OVA). After removing all conventional APCs from the peripheral blood of immunised pigs, the remaining lymphocytes still proliferated when stimulated with OVA. When gammadelta T cells were further depleted, OVA specific proliferation was abolished, but reconstitution with gammadelta T cells restored proliferation. The proliferation was blocked by monoclonal antibodies (mAb) against MHC class II or CD4, and by pre-treatment of gammadelta T cells with chloroquine. These results indicate that a sub-population of circulating porcine gammadelta T cells act as APCs and present antigen via MHC class II.

The adjuvant potential of synthetic alkylglycerols.

Science.gov (United States)

Acevedo, Reinaldo; Gil, Danay; del Campo, Judith; Bracho, Gustavo; Valdés, Yolanda; Pérez, Oliver

2006-04-12

Alkylglycerols (AGs) have shown immune stimulant and adjuvant activity in many studies, but natural sources are not so accessible and their extraction from them is very complicated. Therefore, a group of chemists at IFAL have synthesized AG analogs. The aim of this work was to evaluate the adjuvant potential of different synthetic AGs. A mix of ovoalbumin (Ova) and AGs increase anti-Ova IgG antibodies production in sera of immunized mice. The predominant subclass was IgG1 although higher levels of IgG2a were observed as the carbon chain length of AGs increased. AGs also induced the production of IL-12 and nitric oxide (NO) in the U937 human histiocyte and J774 mouse macrophage cell lines, respectively. These results indicate that synthetic AGs are effective adjuvants for the standardized antigen, Ova.

Isolation and characterization of antigen-Ia complexes involved in T cell recognition

DEFF Research Database (Denmark)

Buus, S; Sette, A; Colon, S M

1986-01-01

Using equilibrium dialysis, it has been previously demonstrated that immunogenic peptides bind specifically to the Ia molecules serving as restriction elements in the immune response to these antigens. Using gel filtration to study the formation of ovalbumin (OVA) peptide-I-Ad complexes, it is he......Using equilibrium dialysis, it has been previously demonstrated that immunogenic peptides bind specifically to the Ia molecules serving as restriction elements in the immune response to these antigens. Using gel filtration to study the formation of ovalbumin (OVA) peptide-I-Ad complexes...... with glutaraldehyde revealed that the ovalbumin peptide was cross-linked solely to the alpha chain of I-Ad. Planar membranes containing I-Ad-OVA complexes stimulated a T cell response with 2 X 10(4) less antigen than required when uncomplexed antigen was used, thus demonstrating the biologic importance...

Comparison of the changes of the antigenicities of a hen's egg albumin by a gamma and an electron beam irradiation

Energy Technology Data Exchange (ETDEWEB)

Lee, Ju-Woon [Department of Radiation Food Science and Biotechnology, Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185, Jeonbuk (Korea, Republic of); Seo, Ji-Hyun [Department of Radiation Food Science and Biotechnology, Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185, Jeonbuk (Korea, Republic of); Kim, Jae-Hun [Department of Radiation Food Science and Biotechnology, Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185, Jeonbuk (Korea, Republic of); Lee, Soo-Young [Department of Pediatrics, Ajou University School of medicine, Suwon 442-749 (Korea, Republic of); Byun, Myung-Woo [Department of Radiation Food Science and Biotechnology, Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185, Jeonbuk (Korea, Republic of)]. E-mail: mwbyun@kaeri.re.kr

2007-05-15

The study was conducted to compare the radiation types of a gamma ray and an electron beam for the inhibition and reduction of a food allergy. OVA (2 mg/ml) were irradiated at 3, 5, 7 and 10 kGy. Patterns detected by the SDS-PAGE and an immunoblot showed that the intact OVA band disappeared and that it was dependant upon the radiation doses regardless of the radiation types. Binding abilities of the irradiated OVA against the monoclonal IgG and the egg allergic patients' IgE decreased due to a conformational change of the epitope, but differences from using the two different radiation types were not observed. The results indicate that both the radiation types can be used for an inhibition and a reduction of a food allergy regardless of the radiation types.

Distribution of schistosomiasis and soil transmitted helminthiasis in Zimbabwe: towards a national plan of action for control and elimination.

Science.gov (United States)

Midzi, Nicholas; Mduluza, Takafira; Chimbari, Moses J; Tshuma, Clement; Charimari, Lincoln; Mhlanga, Gibson; Manangazira, Portia; Munyati, Shungu M; Phiri, Isaac; Mutambu, Susan L; Midzi, Stanley S; Ncube, Anastancia; Muranzi, Lawrence P; Rusakaniko, Simbarashe; Mutapi, Francisca

2014-08-01

Schistosomiasis and STH are among the list of neglected tropical diseases considered for control by the WHO. Although both diseases are endemic in Zimbabwe, no nationwide control interventions have been implemented. For this reason in 2009 the Zimbabwe Ministry of Health and Child Care included the two diseases in the 2009-2013 National Health Strategy highlighting the importance of understanding the distribution and burden of the diseases as a prerequisite for elimination interventions. It is against this background that a national survey was conducted. A countrywide cross-sectional survey was carried out in 280 primary schools in 68 districts between September 2010 and August 2011. Schistosoma haematobium was diagnosed using the urine filtration technique. Schistosoma mansoni and STH (hookworms, Trichuris trichiura, Ascaris lumbricoides) were diagnosed using both the Kato Katz and formol ether concentration techniques. Schistosomiasis was more prevalent country-wide (22.7%) than STH (5.5%). The prevalence of S. haematobium was 18.0% while that of S. mansoni was 7.2%. Hookworms were the most common STH with a prevalence of 3.2% followed by A. lumbricoides and T. trichiura with prevalence of 2.5% and 0.1%, respectively. The prevalence of heavy infection intensity as defined by WHO for any schistosome species was 5.8% (range 0%-18.3% in districts). Only light to moderate infection intensities were observed for STH species. The distribution of schistosomiasis and STH varied significantly between provinces, districts and schools (p<0.001). Overall, the prevalence of co-infection with schistosomiasis and STH was 1.5%. The actual co-endemicity of schistosomiasis and STH was observed in 43 (63.2%) of the 68 districts screened. This study provided comprehensive baseline data on the distribution of schistosomiasis and STH that formed the basis for initiating a national control and elimination programme for these two neglected tropical diseases in Zimbabwe.

[Schistosomiasis and soil-transmitted helminthiasis among schoolchildren of Nikki and Pèrèrè, two northeastern towns of Benin].

Science.gov (United States)

Ibikounlé, M; Gbédjissi, L G; Ogouyèmi-Hounto, A; Batcho, W; Kindé-Gazard, D; Massougbodji, A

2014-08-01

Infection with schistosomiasis and soil-transmitted helminthiasis are widespread in sub-Saharan Africa and the burden of disease associated with parasites is enormous. A study was performed to determine the transmission and prevalence of human schistosomiasis and soil-transmitted helminthiasis among school children of Nikki and Perere, two north eastern towns of Benin, bordering Republic of Nigeria. Parasitological investigations by urine filtration and Kato-Katz conducted on 1,344 school children indicated a mean prevalence of S. haematobium and S. mansoni 48.44% and 0%, respectively, in the children of Nikki area and 45.24% and 4.11% in Perere area. Only schoolchildren of Sonon locality were infected by S. mansoni with a mean prevalence rate of 36.24%. KatoKatz tests releaved five species of soil-transmitted helminths: Ankylostoma duodenale (8.16% and 6.73%), Ascaris lumbricoides (6.26% and 2.30%), Enterobius vermicularis (1.09% and 1.97%), Trichuris trichiura (1.97% and 1.90%) and Strongyloides stercoralis (2.04% and 0.99%), respectively, in the schoolchildren of Nikki and Perere areas. The malacological investigations carried out in the freshwater points of each visited locality highlighted the presence of four species of freshwater snails known as intermediate host of schistosome: Biomphalaria pfeifferi, Bulinus forskalii, B. globosus and B. truncatus.Two B. globosus and B. pfeifferi collected in Sonon locality were naturally infected by schistosome, indicated the importance of their two species of snail in schistosome transmission cycle.

International Journal of Health Research

African Journals Online (AJOL)

Erah

2009-12-28

Dec 28, 2009 ... forum for the communication and evaluation of data, methods and findings in health sciences and related disciplines. .... al [8] for the detection of schistosome DNA in faeces. ..... save the inhabitants from the socio- economic ...

Pattern and Risk Factors of Urinary Bladder Neoplasms in ...

African Journals Online (AJOL)

It poses biologic and clinical challenges. ... Conclusion: There is significant relationship between urinary schistosomal infestation and the development of squamous cell carcinoma of the urinary bladder among Sudanese patients. Keywords: Urinary Bladder, Transitional Cell Carcinoma, Squamous Cell Carcinoma

EAMJ Nov. Effects.indd

African Journals Online (AJOL)

2008-11-11

Nov 11, 2008 ... pfeifferi and the Bulinus spp the intermediate host for schistosome at all canoe landing sites at Kigungu, these ..... transmission site and facilitates prompt reporting to the health ... This study received financial assistant from the ...

Lactococcus lactis NCC 2287 Alleviates Food Allergic Manifestations in Sensitized Mice by Reducing IL-13 Expression Specifically in the Ileum

Directory of Open Access Journals (Sweden)

Adrian W. Zuercher

2012-01-01

Full Text Available Objective. Utilizing a food allergy murine model, we have investigated the intrinsic antiallergic potential of the Lactococcus lactis NCC 2287 strain. Methods. BALB/c mice were sensitized at weekly intervals with ovalbumin (OVA plus cholera toxin (CT by the oral route for 7 weeks. In this model, an oral challenge with a high dose of OVA at the end of the sensitization period leads to clinical symptoms. Lactococcus lactis NCC 2287 was given to mice via the drinking water during sensitization (prevention phase or after sensitization (management phase. Results. Lactococcus lactis NCC 2287 administration to sensitized mice strikingly reduced allergic manifestations in the management phase upon challenge, when compared to control mice. No preventive effect was observed with the strain. Lactococcus lactis NCC 2287 significantly decreased relative expression levels of the Th-2 cytokine, IL-13, and associated chemokines CCL11 (eotaxin-1 and CCL17 (TARC in the ileum. No effect was observed in the jejunum. Conclusion/Significance. These results taken together designate Lactococcus lactis NCC 2287 as a candidate probiotic strain appropriate in the management of allergic symptoms.

Застосування полімеразної ланцюгової реакції у контролі паразитарної ситуації

OpenAIRE

Волошина, Н. О.; Voloshyna, N.

2012-01-01

For the control of the parasitic situation with reference to the animal parasitoses which are actual in the social aspect a method using the polimeraze chain reaction for detecting and identifying ova of parasitic nematodes of domestic beasts of prey (Toxocara canis, Toxocara cati and Taxascaris leonine) in the environment has been developed. Oligonucleotide primers have been developed and synthesized; conditions of their work have been theoretically calculated and optimized in practice. The ...

The effects of acute and chronic estrogen deficiency on glucose and lipid profile in ovariectomized rats

OpenAIRE

Rabie P; Namjoo AR

2017-01-01

Background and aims: Ovariectomy is a standard experimental model of menopause in rodent to investigate postmenopausal women. The aim of this study was to evaluate effects acute and chronic estrogen deficiency on lipid profile and glucose serum in ovariectomized (OVX) rats. Methods: In this experimental study, Twenty-four adult female Wistar rats were divided into three groups of eight rats. The first group: sham-control, Second group: ovariectomized rats (for five weeks), Third group: Ova...

Fate of challenge schistosomula in the murine anti-schistosome vaccine model

International Nuclear Information System (INIS)

Von Lichtenberg, F.; Correa-Oliveira, R.; Sher, A.

1985-01-01

Mice exposed to irradiated cercariae of Schistosoma mansoni develop a partial resistance to subsequent parasite challenge. In this study the authors utilized histopathologic methods to investigate the fate of both the immunizing and challenge cercariae in C57BL/6J mice. After immunization by percutaneous infection, a large number of the 50 Kr irradiated organisms could be detected in tissue sections of lung. However, as early as 2 weeks after immunization, the majority of these schistosomula apparently had died, leaving residual inflammatory foci. The numbers of these foci then gradually declined during the next 4 weeks of examination. Cercarial challenge of mice vaccinated 4 weeks previously provoked an intense eosinophil-enriched inflammatory response in percutaneously exposed ear pinnae. Despite these pronounced tissue reactions, no evidence of significant parasite damage or attrition was detected in this migration site. In contrast, schistosomula arriving in the lungs of vaccinated mice produced a greater number of residual inflammatory foci than did larvae appearing in the lungs of normal mice. In addition, challenge schistosomula were cleared from the lungs of vaccinated mice at a slower rate than they were from the lungs of control mice. These observations suggest that the lung is a major site of parasite attrition for both immunizing and challenge infections in the mouse irradiated vaccine model

Innate, adaptive and regulatory responses in schistosomiasis: Relationship to allergy

NARCIS (Netherlands)

Hartgers, F.C.; Smits, H.H.; Kleij, D. van der; Yazdanbakhsh, M.

2006-01-01

Helminth infections have profound effects on the immune system. Here, recent insights in the molecular interactions between schistosomes and the host are described with respect to adaptive but also with respect to innate immune responses. Furthermore, the different mechanisms of immune

Organomegaly in Mali before and after praziquantel treatment. A possible association with Schistosoma haematobium

DEFF Research Database (Denmark)

Stecher, Chalotte Willemann; Madsen, Henry; Wilson, Shona

2017-01-01

Continuous exposure to schistosome-infested water results in acute and chronic morbidity in all ages. We analysed occurence of organomegaly via ultrasonography and investigated a possible additive effect of dual-dose drug administration in 401 Schistosoma haematobium infected individuals from...

Rapidly boosted Plasma IL-5 induced by treatment of human Schistosomiasis haematobium is dependent on antigen dose, IgE and eosinophils

DEFF Research Database (Denmark)

Wilson, Shona; Jones, Frances M.; Fofana, Hassan K. M.

2013-01-01

IgE specific to worm antigen (SWA) and pre-treatment eosinophil number, are associated with human immunity to re-infection with schistosomes after chemotherapeutic treatment. Treatment significantly elevates circulating IL-5 24-hr post-treatment of Schistosoma mansoni. Here we investigate...

Transmission studies of intestinal schistosomiasis in Lake Albert, Uganda and experimental compatibility of local Biomphalaria spp

DEFF Research Database (Denmark)

Kazibwe, F.; Makanga, B.; Rubaire-Akiiki, C.

2010-01-01

schistosome-snail interactions and confirmation of transmission foci. Cercarial shedding patterns of field-caught Biomphalaria spp., as identified by morphology, were hourly observed over a ten day period and showed that Biomphalaria stanleyi produced significantly more cercariae than Biomphalaria sudanica...

[Oncomelania hupensis snail distribution in working areas of Yangtze River hydrologic agencies located in middle and lower reaches of Yangtze River in 2016].

Science.gov (United States)

Min, Xu; Suo-Xin, Huang; Zheng-Yuan, Zhao; Ben-Jiao, Hu; Jun, Fu; Si-Min, Dai; Li-Hong, Wen

2016-10-13

To understand the Oncomelania hupensis snail distribution in the working areas of Yangtze River hydrologic agencies located in the middle and lower reaches of the Yangtze River in 2016, so as to provide the evidence for assessing the risk of schistosome infection of hydrological workers and establishing the control strategies. The suspicious environments with O. hupensis snails in the above working areas were selected as study areas, and the snail situation was surveyed by the system sampling method combined with the environmental sampling method. The survey data were collected and analyzed statistically. Totally 19 working areas from 17 hydrological agencies were selected as the investigation sites, among which, 10 working areas from 9 agencies were found with O. hupensis snail distribution. The constituent ratio of the areas with snails reached to 38.81% of the investigation areas, the occurrence rate of frames with snails was 3.08%, and the average density of living snails was 0.07 /0.1 m 2 . By comparison, the average density of living snails and occurrence rate of frames with snails in hydrological agencies under the jurisdiction of the Middle Reaches Administrative Bureau were the most serious among three administrative bureaus of the Yangtze River Water Resources Commission. There are various degrees of O. hupensis breeding in the working areas of hydrological agencies located in the middle and lower reaches of the Yangtze River, and the hydrological workers are facing with the risk of schistosome infection.

New insights into the genetic diversity of Schistosoma mansoni and S. haematobiumin Yemen.

Science.gov (United States)

Sady, Hany; Al-Mekhlafi, Hesham M; Webster, Bonnie L; Ngui, Romano; Atroosh, Wahib M; Al-Delaimy, Ahmed K; Nasr, Nabil A; Chua, Kek Heng; Lim, Yvonne A L; Surin, Johari

2015-10-20

Human schistosomiasis is a neglected tropical disease of great importance that remains highly prevalent in Yemen, especially amongst rural communities. In order to investigate the genetic diversity of human Schistosoma species, a DNA barcoding study was conducted on S. mansoni and S. haematobium in Yemen. A cross-sectional study was conducted to collect urine and faecal samples from 400 children from five provinces in Yemen. The samples were examined for the presence of Schistosoma eggs. A partial fragment of the schistosome cox1 mitochondrial gene was analysed from each individual sample to evaluate the genetic diversity of the S. mansoni and S. haematobium infections. The data was also analysed together with previous published cox1 data for S. mansoni and S. haematobium from Africa and the Indian Ocean Islands. Overall, 31.8 % of participants were found to be excreting schistosome eggs in either the urine or faeces (8.0 % S. mansoni and 22.5 % S. haematobium). Nineteen unique haplotypes of S. mansoni were detected and split into four lineages. Furthermore, nine unique haplotypes of S. haematobium were identified that could be split into two distinct groups. This study provides novel and interesting insights into the population diversity and structure of S. mansoni and S. haematobium in Yemen. The data adds to our understanding of the evolutionary history and phylogeography of these devastating parasites whilst the genetic information could support the control and monitoring of urogenital and intestinal schistosomiasis in these endemic areas.

A proteomics panel for predicting optimal primary cytoreduction in stage III/IV ovarian cancer

DEFF Research Database (Denmark)

Risum, Signe; Høgdall, Estrid; Engelholm, Svend A

2009-01-01

for CA-125. In addition, serum was analyzed for 7 biomarkers using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry. These biomarkers were combined into a single-valued ovarian-cancer-risk index (OvaRI). CA-125 and OvaRI were evaluated as predictors of cytoreduction in 75......The objective of this prospective study was to evaluate CA-125 and a 7-marker panel as predictors of incomplete primary cytoreduction in patients with stage III/IV ovarian cancer (OC). From September 2004 to January 2008, serum from 201 patients referred to surgery for a pelvic tumor was analyzed...... stage III/IV patients using receiver operating characteristic curves. Complete primary cytoreduction (no macroscopic residual disease) was achieved in 31% (23/75) of the patients. The area under the receiver operating characteristic curve was 0.66 for CA-125 and 0.75 for OvaRI. The sensitivity...

Microcontainers as an oral delivery system for spray dried cubosomes containing ovalbumin

DEFF Research Database (Denmark)

Nielsen, Line Hagner; Rades, Thomas; Boyd, Ben

2017-01-01

The purpose of this study was to prepare cubosomes encapsulating the model antigen ovalbumin (OVA) via spray drying, and to characterise such cubosomes with a view for their potential application in oral vaccine delivery. Furthermore the cubosome formulation was loaded into polymeric...... microcontainers intended as an oral drug delivery system. The cubosomes consisted of commercial glyceryl monooleate, Dimodan®, containing OVA and were surrounded with a dextran shell prepared by spray drying. Cryo-TEM was used to confirm that cubosomes were formed after hydration of the spray dried precursor...... the cubosomes and microcontainers occurred at pH 6.8, releasing 44.1±5.6% of the OVA in 96h. Small-angle X-ray scattering (SAXS) revealed that the 'dry' particles possessed an internal ordered lipid structure (lamellar and inverse micellar phase) by virtue of a small amount of residual water, and after...

Molecular epidemiology and pathology of spirorchiid infection in green sea turtles (Chelonia mydas

Directory of Open Access Journals (Sweden)

Phoebe A. Chapman

2017-04-01

Full Text Available Spirorchiid blood fluke infections affect endangered turtle populations globally, and are reported as a common cause of mortality in Queensland green sea turtles. Both the flukes and their ova are pathogenic and can contribute to the stranding or death of their host. Of particular interest are ova-associated brain lesions, which have been associated with host neurological deficits. Accurate estimations of disease frequency and the relative effect of infection relating to different spirorchiid species are made difficult by challenges in morphological identification of adults of some genera, and a lack of species-level identifying features for ova. A new specifically designed molecular assay was used to detect and identify cryptic spirorchiids and their ova in Queensland green sea turtle tissues collected from 2011 to 2014 in order to investigate epidemiology, tissue tropisms and pathology. Eight spirorchiid genotypes were detected in 14 distinct tissues, including multiple tissues for each. We found no evidence of a characteristic pathway of the eggs to the exterior; instead the results suggest that a high proportion of eggs become lost in dead-end tissues. The most common lesions observed were granulomas affecting most organs with varying severity, followed by arteritis and thrombi in the great vessels. The number of spirorchiid types detected increased with the presence and severity of granulomatous lesions. However, compared with other organs the brain showed relatively low levels of spirorchiid diversity. An inverse relationship between host age and spirorchiid diversity was evident for the liver and kidneys, but no such relationship was evident for other organs. Molecular data in this study, the first of its kind, provides the first species-level examination of spirorchiid ova and associated pathology, and paves the way for the future development of targeted ante-mortem diagnosis of spirorchiidiasis.

Effects of maternal exposure to di(2-ethylhexyl)phthalate (DEHP) during pregnancy on susceptibility to neonatal asthma

Energy Technology Data Exchange (ETDEWEB)

Shin, In-Sik; Lee, Mee-Young [Basic Herbal Medicine Research Group, Korea Institute of Oriental Medicine, 483 Expo-ro, Yusung-gu, Daejeon 305-811 (Korea, Republic of); Cho, Eun-Sang [College of Veterinary Medicine, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon 305-764 (Korea, Republic of); Choi, Eun-young [College of Nursing and Health, Kongju National University, 56 Gongju Daehak-ro, Gongju, Chungnam 314-701 (Korea, Republic of); Son, Hwa-Young [College of Veterinary Medicine, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon 305-764 (Korea, Republic of); Lee, Kyoung-Youl, E-mail: youl10@hanmail.net [College of Nursing and Health, Kongju National University, 56 Gongju Daehak-ro, Gongju, Chungnam 314-701 (Korea, Republic of)

2014-02-01

Di(2-ethylhexyl) phthalate (DEHP) is used as a plasticizer and is widely dispersed in the environment. In this study, we investigated the effects of maternal exposure to DEHP during pregnancy on neonatal asthma susceptibility using a murine model of asthma induced by ovalbumin (OVA). Pregnant BALB/c mice received DEHP from gestation day 13 to lactation day 21. Their offspring were sensitized on postnatal days (PNDs) 9 and 15 by intraperitoneal injection of 0.5 μg OVA with 200 μg aluminum hydroxide. On PNDs 22, 23 and 24, live pups received an airway challenge of OVA for 30 min. Offspring from pregnant mice that received DEHP showed reductions in inflammatory cell count, interleukin (IL)-4, IL-13, and eotaxin in their bronchoalveolar lavage fluid and in total immunoglobulin E and OVA-specific IgE in their plasma compared with offspring from pregnant mice that did not receive DEHP treatment. These results were consistent with histological analysis and immunoblotting. Maternal exposure to DEHP reduces airway inflammation and mucus production in offspring, with a decrease in inducible nitric oxide synthase (iNOS) in the lung tissue. This study suggests that maternal exposure to DEHP during pregnancy reduces asthmatic responses induced by OVA challenge in offspring. These effects were considered to be closely related to the suppression of Th2 immune responses and iNOS expression. - Highlights: • Maternal exposure to di(2-ethylhexyl)phthalate reduces asthmatic response in pups. • Di(2-ethylhexyl)phthalate reduces eosinophilia induced by ovalbumin exposure. • Di(2-ethylhexyl)phthalate reduces T-helper type 2 cytokine production. • Di(2-ethylhexyl)phthalate attenuates airway inflammation and mucus production. • Di(2-ethylhexyl)phthalate suppresses inducible nitric oxide synthase in lung tissue.

Effects of maternal exposure to di(2-ethylhexyl)phthalate (DEHP) during pregnancy on susceptibility to neonatal asthma

International Nuclear Information System (INIS)

Shin, In-Sik; Lee, Mee-Young; Cho, Eun-Sang; Choi, Eun-young; Son, Hwa-Young; Lee, Kyoung-Youl

2014-01-01

Di(2-ethylhexyl) phthalate (DEHP) is used as a plasticizer and is widely dispersed in the environment. In this study, we investigated the effects of maternal exposure to DEHP during pregnancy on neonatal asthma susceptibility using a murine model of asthma induced by ovalbumin (OVA). Pregnant BALB/c mice received DEHP from gestation day 13 to lactation day 21. Their offspring were sensitized on postnatal days (PNDs) 9 and 15 by intraperitoneal injection of 0.5 μg OVA with 200 μg aluminum hydroxide. On PNDs 22, 23 and 24, live pups received an airway challenge of OVA for 30 min. Offspring from pregnant mice that received DEHP showed reductions in inflammatory cell count, interleukin (IL)-4, IL-13, and eotaxin in their bronchoalveolar lavage fluid and in total immunoglobulin E and OVA-specific IgE in their plasma compared with offspring from pregnant mice that did not receive DEHP treatment. These results were consistent with histological analysis and immunoblotting. Maternal exposure to DEHP reduces airway inflammation and mucus production in offspring, with a decrease in inducible nitric oxide synthase (iNOS) in the lung tissue. This study suggests that maternal exposure to DEHP during pregnancy reduces asthmatic responses induced by OVA challenge in offspring. These effects were considered to be closely related to the suppression of Th2 immune responses and iNOS expression. - Highlights: • Maternal exposure to di(2-ethylhexyl)phthalate reduces asthmatic response in pups. • Di(2-ethylhexyl)phthalate reduces eosinophilia induced by ovalbumin exposure. • Di(2-ethylhexyl)phthalate reduces T-helper type 2 cytokine production. • Di(2-ethylhexyl)phthalate attenuates airway inflammation and mucus production. • Di(2-ethylhexyl)phthalate suppresses inducible nitric oxide synthase in lung tissue

Turmeric (Curcuma longa) attenuates food allergy symptoms by regulating type 1/type 2 helper T cells (Th1/Th2) balance in a mouse model of food allergy.

Science.gov (United States)

Shin, Hee Soon; See, Hye-Jeong; Jung, Sun Young; Choi, Dae Woon; Kwon, Da-Ae; Bae, Min-Jung; Sung, Ki-Seung; Shon, Dong-Hwa

2015-12-04

Turmeric (Curcuma longa) has traditionally been used to treat pain, fever, allergic and inflammatory diseases such as bronchitis, arthritis, and dermatitis. In particular, turmeric and its active component, curcumin, were effective in ameliorating immune disorders including allergies. However, the effects of turmeric and curcumin have not yet been tested on food allergies. Mice were immunized with intraperitoneal ovalbumin (OVA) and alum. The mice were orally challenged with 50mg OVA, and treated with turmeric extract (100mg/kg), curcumin (3mg/kg or 30 mg/kg) for 16 days. Food allergy symptoms including decreased rectal temperature, diarrhea, and anaphylaxis were evaluated. In addition, cytokines, immunoglobulins, and mouse mast cell protease-1 (mMCP-1) were evaluated using ELISA. Turmeric significantly attenuated food allergy symptoms (decreased rectal temperature and anaphylactic response) induced by OVA, but curcumin showed weak improvement. Turmeric also inhibited IgE, IgG1, and mMCP-1 levels increased by OVA. Turmeric reduced type 2 helper cell (Th2)-related cytokines and enhanced a Th1-related cytokine. Turmeric ameliorated OVA-induced food allergy by maintaining Th1/Th2 balance. Furthermore, turmeric was confirmed anti-allergic effect through promoting Th1 responses on Th2-dominant immune responses in immunized mice. Turmeric significantly ameliorated food allergic symptoms in a mouse model of food allergy. The turmeric as an anti-allergic agent showed immune regulatory effects through maintaining Th1/Th2 immune balance, whereas curcumin appeared immune suppressive effects. Therefore, we suggest that administration of turmeric including various components may be useful to ameliorate Th2-mediated allergic disorders such as food allergy, atopic dermatitis, and asthma. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Regulation of allergic airway inflammation by adoptive transfer of CD4+ T cells preferentially producing IL-10.

Science.gov (United States)

Matsuda, Masaya; Doi, Kana; Tsutsumi, Tatsuya; Fujii, Shinya; Kishima, Maki; Nishimura, Kazuma; Kuroda, Ikue; Tanahashi, Yu; Yuasa, Rino; Kinjo, Toshihiko; Kuramoto, Nobuyuki; Mizutani, Nobuaki; Nabe, Takeshi

2017-10-05

Anti-inflammatory pharmacotherapy for asthma has mainly depended on the inhalation of glucocorticoids, which non-specifically suppress immune responses. If the anti-inflammatory cytokine interleukin (IL)-10 can be induced by a specific antigen, asthmatic airway inflammation could be suppressed when individuals are exposed to the antigen. The purpose of this study was to develop cellular immunotherapeutics for atopic diseases using IL-10-producing CD4 + T cells. Spleen cells isolated from ovalbumin (OVA)-sensitized mice were cultured with the antigen, OVA and growth factors, IL-21, IL-27 and TGF-β for 7 days. After the 7-day culture, the CD4 + T cells were purified using a murine CD4 magnetic beads system. When the induced CD4 + T cells were stimulated by OVA in the presence of antigen-presenting cells, IL-10 was preferentially produced in vitro. When CD4 + T cells were adoptively transferred to OVA-sensitized mice followed by intratracheal OVA challenges, IL-10 was preferentially produced in the serum and bronchoalveolar lavage fluid in vivo. IL-10 production coincided with the inhibition of eosinophilic airway inflammation and epithelial mucus plugging. Most of the IL-10-producing CD4 + T cells were negative for Foxp3 and GATA-3, transcription factors of naturally occurring regulatory T cells and Th2 cells, respectively, but double positive for LAG-3 and CD49b, surface markers of inducible regulatory T cells, Tr1 cells. Collectively, most of the induced IL-10-producing CD4 + T cells could be Tr1 cells, which respond to the antigen to produce IL-10, and effectively suppressed allergic airway inflammation. The induced Tr1 cells may be useful for antigen-specific cellular immunotherapy for atopic diseases. Copyright © 2017 Elsevier B.V. All rights reserved.

The existence of fertile hybrids of closely related model earthworm species, Eisenia andrei and E. fetida.

Directory of Open Access Journals (Sweden)

Barbara Plytycz

Full Text Available Lumbricid earthworms Eisenia andrei (Ea and E. fetida (Ef are simultaneous hermaphrodites with reciprocal insemination capable of self-fertilization while the existence of hybridization of these two species was still debatable. During the present investigation fertile hybrids of Ea and Ef were detected. Virgin specimens of Ea and Ef were laboratory crossed (Ea+Ef and their progeny was doubly identified. 1 -identified by species-specific maternally derived haploid mitochondrial DNA sequences of the COI gene being either 'a' for worms hatched from Ea ova or 'f' for worms hatched from Ef ova. 2 -identified by the diploid maternal/paternal nuclear DNA sequences of 28s rRNA gene being either 'AA' for Ea, 'FF' for Ef, or AF/FA for their hybrids derived either from the 'aA' or 'fF' ova, respectively. Among offspring of Ea+Ef pairs in F1 generation there were mainly aAA and fFF earthworms resulted from the facilitated self-fertilization and some aAF hybrids from aA ova but none fFA hybrids from fF ova. In F2 generation resulting from aAF hybrids mated with aAA a new generations of aAA and aAF hybrids were noticed, while aAF hybrids mated with fFF gave fFF and both aAF and fFA hybrids. Hybrids intercrossed together produced plenty of cocoons but no hatchlings independently whether aAF+aAF or aAF+fFA were mated. These results indicated that Ea and Ef species, easy to maintain in laboratory and commonly used as convenient models in biomedicine and ecotoxicology, may also serve in studies on molecular basis of interspecific barriers and mechanisms of introgression and speciation. Hypothetically, their asymmetrical hybridization can be modified by some external factors.

Clonorchis sinensis-derived total protein attenuates airway inflammation in murine asthma model by inducing regulatory T cells and modulating dendritic cell functions

International Nuclear Information System (INIS)

Jeong, Young-Il; Kim, Seung Hyun; Ju, Jung Won; Cho, Shin Hyeong; Lee, Won Ja; Park, Jin Wook; Park, Yeong-Min; Lee, Sang Eun

2011-01-01

Highlights: → Treatment with Clonorchis sinensis-derived total protein attenuates OVA-induced airway inflammation and AHR to methacholine. → Induction of CD4 + CD25 + Foxp3 + T cells and IL-10 along with suppression of splenocyte proliferation by C. sinensis-derived total protein. → C. sinensis-derived total protein interferes with the expression of co-stimulatory molecules in DCs. -- Abstract: Asthma is characterized by Th2-mediated inflammation, resulting in airway hyperresponsiveness (AHR) through airway remodeling. Recent epidemiological and experimental reports have suggested an inverse relationship between the development of allergy and helminth infections. Infection by Clonorchis sinensis, a liver fluke that resides in the bile duct of humans, is endemic predominantly in Asia including Korea and China. Using a murine model for asthma, we investigated the effects of C. sinensis-derived total protein (Cs-TP) on allergen-induced airway inflammation and the mechanism underlying the protective effects of Cs-TP administration on asthma. Treatment with Cs-TP attenuated OVA-induced airway inflammation and methacholine-induced AHR, as well as eosinophilia development, lymphocyte infiltration into the lung, and goblet cell metaplasia. This protective effect of Cs-TP is associated with markedly reduced OVA-specific IgE and Th1/Th2 cytokine production. Moreover, Cs-TP increased the number of CD4 + CD25 + Foxp3 + regulatory T (Treg) cells as well as their suppressive activity. In fact, proliferation of OVA-restimulated splenocytes was suppressed significantly. Cs-TP also inhibited the expression of such co-stimulatory molecules as CD80, CD86, and CD40 in LPS- or OVA-stimulated dendritic cells (DCs), suggesting that Cs-TP could interfere with the capacity of airway DCs to prime naive T cells. These data demonstrate the capacity of C. sinensis to ameliorate allergic asthma and broaden our understanding of the paradoxical relationship between the allergic immune

Exposure to particulate hexavalent chromium exacerbates allergic asthma pathology

International Nuclear Information System (INIS)

Schneider, Brent C.; Constant, Stephanie L.; Patierno, Steven R.; Jurjus, Rosalyn A.; Ceryak, Susan M.

2012-01-01

Airborne hexavalent chromate, Cr(VI), has been identified by the Environmental Protection Agency as a possible health threat in urban areas, due to the carcinogenic potential of some of its forms. Particulate chromates are produced in many different industrial settings, with high levels of aerosolized forms historically documented. Along with an increased risk of lung cancer, a high incidence of allergic asthma has been reported in workers exposed to certain inhaled particulate Cr(VI) compounds. However, a direct causal association between Cr(VI) and allergic asthma has not been established. We recently showed that inhaled particulate Cr(VI) induces an innate neutrophilic inflammatory response in BALB/c mice. In the current studies we investigated how the inflammation induced by inhaled particulate Cr(VI) might alter the pathology of an allergic asthmatic response. We used a well-established mouse model of allergic asthma. Groups of ovalbumin protein (OVA)-primed mice were challenged either with OVA alone, or with a combination of OVA and particulate zinc chromate, and various parameters associated with asthmatic responses were measured. Co-exposure to particulate Cr(VI) and OVA mediated a mixed form of asthma in which both eosinophils and neutrophils are present in airways, tissue pathology is markedly exacerbated, and airway hyperresponsiveness is significantly increased. Taken together these findings suggest that inhalation of particulate forms of Cr(VI) may augment the severity of ongoing allergic asthma, as well as alter its phenotype. Such findings may have implications for asthmatics in settings in which airborne particulate Cr(VI) compounds are present at high levels. -- Highlights: ► Allergic asthma correlated with exposure to certain inhaled particulate chromates. ► Direct causal association between Cr(VI) and allergic asthma not established. ► Cr exacerbated pathology and airway hyperresponsiveness in an OVA-challenged mouse. ► Particulate Cr

Exposure to particulate hexavalent chromium exacerbates allergic asthma pathology

Energy Technology Data Exchange (ETDEWEB)

Schneider, Brent C. [Department of Microbiology, Immunology and Tropical Medicine, The George Washington University, Washington, DC 20037 (United States); Department of Pharmacology and Physiology, The George Washington University, Washington, DC 20037 (United States); Constant, Stephanie L. [Department of Microbiology, Immunology and Tropical Medicine, The George Washington University, Washington, DC 20037 (United States); Patierno, Steven R. [Department of Pharmacology and Physiology, The George Washington University, Washington, DC 20037 (United States); GW Cancer Institute, The George Washington University, Washington, DC 20037 (United States); Jurjus, Rosalyn A. [Department of Anatomy and Regenerative Biology, The George Washington University, Washington, DC 20037 (United States); Ceryak, Susan M., E-mail: phmsmc@gwumc.edu [Department of Pharmacology and Physiology, The George Washington University, Washington, DC 20037 (United States)

2012-02-15

Airborne hexavalent chromate, Cr(VI), has been identified by the Environmental Protection Agency as a possible health threat in urban areas, due to the carcinogenic potential of some of its forms. Particulate chromates are produced in many different industrial settings, with high levels of aerosolized forms historically documented. Along with an increased risk of lung cancer, a high incidence of allergic asthma has been reported in workers exposed to certain inhaled particulate Cr(VI) compounds. However, a direct causal association between Cr(VI) and allergic asthma has not been established. We recently showed that inhaled particulate Cr(VI) induces an innate neutrophilic inflammatory response in BALB/c mice. In the current studies we investigated how the inflammation induced by inhaled particulate Cr(VI) might alter the pathology of an allergic asthmatic response. We used a well-established mouse model of allergic asthma. Groups of ovalbumin protein (OVA)-primed mice were challenged either with OVA alone, or with a combination of OVA and particulate zinc chromate, and various parameters associated with asthmatic responses were measured. Co-exposure to particulate Cr(VI) and OVA mediated a mixed form of asthma in which both eosinophils and neutrophils are present in airways, tissue pathology is markedly exacerbated, and airway hyperresponsiveness is significantly increased. Taken together these findings suggest that inhalation of particulate forms of Cr(VI) may augment the severity of ongoing allergic asthma, as well as alter its phenotype. Such findings may have implications for asthmatics in settings in which airborne particulate Cr(VI) compounds are present at high levels. -- Highlights: ► Allergic asthma correlated with exposure to certain inhaled particulate chromates. ► Direct causal association between Cr(VI) and allergic asthma not established. ► Cr exacerbated pathology and airway hyperresponsiveness in an OVA-challenged mouse. ► Particulate Cr

Obesity promotes prolonged ovalbumin-induced airway inflammation modulating T helper type 1 (Th1), Th2 and Th17 immune responses in BALB/c mice.

Science.gov (United States)

Silva, F M C; Oliveira, E E; Gouveia, A C C; Brugiolo, A S S; Alves, C C; Correa, J O A; Gameiro, J; Mattes, J; Teixeira, H C; Ferreira, A P

2017-07-01

Clinical and epidemiological studies indicate that obesity affects the development and phenotype of asthma by inducing inflammatory mechanisms in addition to eosinophilic inflammation. The aim of this study was to assess the effect of obesity on allergic airway inflammation and T helper type 2 (Th2) immune responses using an experimental model of asthma in BALB/c mice. Mice fed a high-fat diet (HFD) for 10 weeks were sensitized and challenged with ovalbumin (OVA), and analyses were performed at 24 and 48 h after the last OVA challenge. Obesity induced an increase of inducible nitric oxide synthase (iNOS)-expressing macrophages and neutrophils which peaked at 48 h after the last OVA challenge, and was associated with higher levels of interleukin (IL)-4, IL-9, IL-17A, leptin and interferon (IFN)-γ in the lungs. Higher goblet cell hyperplasia was associated with elevated mast cell influx into the lungs and trachea in the obese allergic mice. In contrast, early eosinophil influx and lower levels of IL-25, thymic stromal lymphopoietin (TSLP), CCL11 and OVA-specific immunoglobulin (IgE) were observed in the obese allergic mice in comparison to non-obese allergic mice. Moreover, obese mice showed higher numbers of mast cells regardless of OVA challenge. These results indicate that obesity affects allergic airway inflammation through mechanisms involving mast cell influx and the release of TSLP and IL-25, which favoured a delayed immune response with an exacerbated Th1, Th2 and Th17 profile. In this scenario, an intense mixed inflammatory granulocyte influx, classically activated macrophage accumulation and intense mucus production may contribute to a refractory therapeutic response and exacerbate asthma severity. © 2017 British Society for Immunology.

Spontaneous food allergy in Was-/- mice occurs independent of FcεRI-mediated mast cell activation.

Science.gov (United States)

Lexmond, W S; Goettel, J A; Sallis, B F; McCann, K; Rings, E H H M; Jensen-Jarolim, E; Nurko, S; Snapper, S B; Fiebiger, E

2017-12-01

Food allergies are a growing health problem, and the development of therapies that prevent disease onset is limited by the lack of adjuvant-free experimental animal models. We compared allergic sensitization in patients with food allergy or Wiskott-Aldrich syndrome (WAS) and defined whether spontaneous disease in Was -/- mice recapitulates the pathology of a conventional disease model and/or human food allergy. Comparative ImmunoCAP ISAC microarray was performed in patients with food allergy or WAS. Spontaneous food allergy in Was -/- mice was compared to an adjuvant-based model in wild-type mice (WT-OVA/alum). Intestinal and systemic anaphylaxis was assessed, and the role of the high-affinity IgE Fc receptor (FcεRI) in allergic sensitization was evaluated using Was -/- Fcer1a -/- mice. Polysensitization to food was detected in both WAS and food-allergic patients which was recapitulated in the Was -/- model. Oral administration of ovalbumin (OVA) in Was -/- mice induced low titers of OVA-specific IgE compared to the WT-OVA/alum model. Irrespectively, 79% of Was -/- mice developed allergic diarrhea following oral OVA challenge. Systemic anaphylaxis occurred in Was -/- mice (95%) with a mortality rate >50%. Spontaneous sensitization and intestinal allergy occurred independent of FcεRI expression on mast cells (MCs) and basophils. Was -/- mice provide a model of food allergy with the advantage of mimicking polysensitization and low food-antigen IgE titers as observed in humans with clinical food allergy. This model will facilitate studies on aberrant immune responses during spontaneous disease development. Our results imply that therapeutic targeting of the IgE/FcεRI activation cascade will not affect sensitization to food. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

Comparative study of colloidal gold and quantum dots as labels for multiplex screening tests for multi-mycotoxin detection

Energy Technology Data Exchange (ETDEWEB)

Foubert, Astrid, E-mail: astrid.foubert@hotmail.com; Beloglazova, Natalia V.; De Saeger, Sarah

2017-02-22

Quantum dots (QDs) and colloidal gold nanoparticles (CG) were evaluated as labels for multiplex lateral flow immunoassay (LFIA) for determination of mycotoxins deoxynivalenol (DON), zearalenone (ZEN) and T2/HT2-toxin (T2/HT2) in cereal matrices. Both developed assays were based on the same immunoreagents (except for the labels), therefore their analytical characteristics could be objectively compared. For both LFIAs antigens (DON-ovalbumin (OVA), ZEN-OVA and T2-OVA) and rabbit anti-mouse immunoglobulin were immobilized on a nitrocellulose membrane as three test lines and one control line, respectively. Depending on the LFIA, monoclonal antibodies (mAb) against DON, ZEN and T2 were conjugated with CdSeS/ZnS QDs or CG. T2 and HT2 were detected by one test line (T2-OVA) with an anti-T2 mAb which showed 110% cross-reactivity with HT2. Both tests were developed in accordance with the legal limits and were developed in such a way that they had the same cut-off limits of 1000 μg kg{sup −1}, 80 μg kg{sup −1} and 80 μg kg{sup −1} for DON, ZEN and T2/HT2, respectively in order to allow a correct comparison. Applicability of these assays was demonstrated by analysis of naturally contaminated wheat samples. The results demonstrate that both the LFIAs can be used as rapid, cost-effective and convenient qualitative tool for on-site screening for simultaneous detection of DON, ZEN and HT2/T2 in wheat without special instrumentation. However, the QD-based LFIA consumed less immunoreagents and was more sensitive and economically beneficial. In addition, the results were easier to interpret, resulting in a lower false negative rate (<5%) which was in good agreement with Commission Decision 2002/657/EC regarding the performance of analytical methods intended for screening purposes. - Highlights: • Development of colloidal gold- and quantum dot-based multiplex lateral flow immunoassay. • Lateral flow immunoassays allow simultaneous detection of four mycotoxins. �

Maximizing Tumor Immunity With Fractionated Radiation

Energy Technology Data Exchange (ETDEWEB)

Schaue, Doerthe, E-mail: dschaue@mednet.ucla.edu [Department of Radiation Oncology, David Geffen School of Medicine at UCLA, Los Angeles, CA (United States); Ratikan, Josephine A.; Iwamoto, Keisuke S.; McBride, William H. [Department of Radiation Oncology, David Geffen School of Medicine at UCLA, Los Angeles, CA (United States)

2012-07-15

Purpose: Technologic advances have led to increased clinical use of higher-sized fractions of radiation dose and higher total doses. How these modify the pathways involved in tumor cell death, normal tissue response, and signaling to the immune system has been inadequately explored. Here we ask how radiation dose and fraction size affect antitumor immunity, the suppression thereof, and how this might relate to tumor control. Methods and Materials: Mice bearing B16-OVA murine melanoma were treated with up to 15 Gy radiation given in various-size fractions, and tumor growth followed. The tumor-specific immune response in the spleen was assessed by interferon-{gamma} enzyme-linked immunospot (ELISPOT) assay with ovalbumin (OVA) as the surrogate tumor antigen and the contribution of regulatory T cells (Tregs) determined by the proportion of CD4{sup +}CD25{sup hi}Foxp3{sup +} T cells. Results: After single doses, tumor control increased with the size of radiation dose, as did the number of tumor-reactive T cells. This was offset at the highest dose by an increase in Treg representation. Fractionated treatment with medium-size radiation doses of 7.5 Gy/fraction gave the best tumor control and tumor immunity while maintaining low Treg numbers. Conclusions: Radiation can be an immune adjuvant, but the response varies with the size of dose per fraction. The ultimate challenge is to optimally integrate cancer immunotherapy into radiation therapy.

Role of the adiponectin binding protein, T-cadherin (Cdh13, in allergic airways responses in mice.

Directory of Open Access Journals (Sweden)

Alison S Williams

Full Text Available Adiponectin is an adipose derived hormone that declines in obesity. We have previously shown that exogenous administration of adiponectin reduces allergic airways responses in mice. T-cadherin (T-cad; Cdh13 is a binding protein for the high molecular weight isoforms of adiponectin. To determine whether the beneficial effects of adiponectin on allergic airways responses require T-cad, we sensitized wildtype (WT, T-cadherin deficient (T-cad(-/- and adiponectin and T-cad bideficient mice to ovalbumin (OVA and challenged the mice with aerosolized OVA or PBS. Compared to WT, T-cad(-/- mice were protected against OVA-induced airway hyperresponsiveness, increases in BAL inflammatory cells, and induction of IL-13, IL-17, and eotaxin expression. Histological analysis of the lungs of OVA-challenged T-cad(-/- versus WT mice indicated reduced inflammation around the airways, and reduced mucous cell hyperplasia. Combined adiponectin and T-cad deficiency reversed the effects of T-cad deficiency alone, indicating that the observed effects of T-cad deficiency require adiponectin. Compared to WT, serum adiponectin was markedly increased in T-cad(-/- mice, likely because adiponectin that is normally sequestered by endothelial T-cad remains free in the circulation. In conclusion, T-cad does not mediate the protective effects of adiponectin. Instead, mice lacking T-cad have reduced allergic airways disease, likely because elevated serum adiponectin levels act on other adiponectin signaling pathways.

Dynamics of antigen presentation to transgene product-specific CD4+ T cells and of Treg induction upon hepatic AAV gene transfer

Directory of Open Access Journals (Sweden)

George Q Perrin

2016-01-01

Full Text Available The tolerogenic hepatic microenvironment impedes clearance of viral infections but is an advantage in viral vector gene transfer, which often results in immune tolerance induction to transgene products. Although the underlying tolerance mechanism has been extensively studied, our understanding of antigen presentation to transgene product-specific CD4+ T cells remains limited. To address this, we administered hepatotropic adeno-associated virus (AAV8 vector expressing cytoplasmic ovalbumin (OVA into wt mice followed by adoptive transfer of transgenic OVA-specific T cells. We find that that the liver-draining lymph nodes (celiac and portal are the major sites of MHC II presentation of the virally encoded antigen, as judged by in vivo proliferation of DO11.10 CD4+ T cells (requiring professional antigen-presenting cells, e.g., macrophages and CD4+CD25+FoxP3+ Treg induction. Antigen presentation in the liver itself contributes to activation of CD4+ T cells egressing from the liver. Hepatic-induced Treg rapidly disseminate through the systemic circulation. By contrast, a secreted OVA transgene product is presented in multiple organs, and OVA-specific Treg emerge in both the thymus and periphery. In summary, liver draining lymph nodes play an integral role in hepatic antigen presentation and peripheral Treg induction, which results in systemic regulation of the response to viral gene products.

Protective Effects of Intratracheally-Administered Bee Venom Phospholipase A2 on Ovalbumin-Induced Allergic Asthma in Mice

Directory of Open Access Journals (Sweden)

Kyung-Hwa Jung

2016-09-01

Full Text Available Asthma is a common chronic disease characterized by bronchial inflammation, reversible airway obstruction, and airway hyperresponsiveness (AHR. Current therapeutic options for the management of asthma include inhaled corticosteroids and β2 agonists, which elicit harmful side effects. In the present study, we examined the capacity of phospholipase A2 (PLA2, one of the major components of bee venom (BV, to reduce airway inflammation and improve lung function in an experimental model of asthma. Allergic asthma was induced in female BALB/c mice by intraperitoneal administration of ovalbumin (OVA on days 0 and 14, followed by intratracheal challenge with 1% OVA six times between days 22 and 30. The infiltration of immune cells, such as Th2 cytokines in the lungs, and the lung histology, were assessed in the OVA-challenged mice in the presence and absence of an intratracheal administration of bvPLA2. We showed that the intratracheal administration of bvPLA2 markedly suppressed the OVA-induced allergic airway inflammation by reducing AHR, overall area of inflammation, and goblet cell hyperplasia. Furthermore, the suppression was associated with a significant decrease in the production of Th2 cytokines, such as IL-4, IL-5, and IL-13, and a reduction in the number of total cells, including eosinophils, macrophages, and neutrophils in the airway.

Total glucosides of paeony attenuated functional maturation of dendritic cells via blocking TLR4/5 signaling in vivo.

Science.gov (United States)

Zhou, Zhou; Lin, Jinpiao; Huo, Rongfen; Huang, Wenkang; Zhang, Jian; Wang, Li; Sun, Yue; Shen, Baihua; Li, Ningli

2012-11-01

It is well known that dendritic cells (DCs) play a critical role in the initiation and development of an immune response. Inhibitory effect on DC maturation alters immune-mediated inflammatory reaction in vivo. Total glucosides of paeony (TGP) are active compounds extracted from the roots of Paeonia lactiflora and have been widely used to ameliorate inflammation in therapy for autoimmune diseases. However, whether TGP act on DC maturation remains unknown. In this study, we investigated the effect of TGP on DC maturation in ovalbumin (OVA) immunized mice. Ear inflammation was inhibited by TGP (150 mgkg(-1), i.p.×11 days) obviously. The antigen presenting capacity of DC derived from TGP-treated mice was arrested. Meanwhile, OVA specific T cell proliferation was inhibited. In addition, we found that maturation of DCs was decreased by TGP treatment. Furthermore, OVA specific T cell proliferation was rescued by the adoptive transfer of mature DCs (mDCs) into TGP treated OVA-challenged mice. The research on the mechanism showed that TGP significantly inhibited activation of TLR4/5 singling. All these results demonstrated that TGP inhibited DC maturation and function by selectively blocking TLR4/5 activation in vivo, which in turn leads to reduce immune-mediated inflammation in vivo, adding a novel mechanism and therapeutic target of TGP for inflammatory and autoimmune disease treatment. Copyright © 2012 Elsevier B.V. All rights reserved.

IL-10 Induction from Implants Delivering Pancreatic Islets and Hyaluronan

Directory of Open Access Journals (Sweden)

Paul L. Bollyky

2013-01-01

Full Text Available Local induction of pro-tolerogenic cytokines, such as IL-10, is an appealing strategy to help facilitate transplantation of islets and other tissues. Here, we describe a pair of implantable devices that capitalize on our recent finding that hyaluronan (HA promotes IL-10 production by activated T cells. The first device is an injectable hydrogel made of crosslinked HA and heparan sulfate loaded with anti-CD3/anti-CD28 antibodies and IL-2. T cells embedded within this hydrogel prior to polymerization go on to produce IL-10 in vivo. The second device is a bioengineered implant consisting of a polyvinyl alcohol sponge scaffold, supportive collagen hydrogel, and alginate spheres mediating sustained release of HA in fluid form. Pancreatic islets that expressed ovalbumin (OVA antigen were implanted within this device for 14 days into immunodeficient mice that received OVA-specific DO.11.10 T cells and a subsequent immunization with OVA peptide. Splenocytes harvested from these mice produced IL-10 upon re-challenge with OVA or anti-CD3 antibodies. Both of these devices represent model systems that will be used, in future studies, to further evaluate IL-10 induction by HA, with the objective of improving the survival and function of transplanted islets in the setting of autoimmune (type 1 diabetes.

Altered fatty acid metabolism and reduced stearoyl-coenzyme a desaturase activity in asthma.

Science.gov (United States)

Rodriguez-Perez, N; Schiavi, E; Frei, R; Ferstl, R; Wawrzyniak, P; Smolinska, S; Sokolowska, M; Sievi, N A; Kohler, M; Schmid-Grendelmeier, P; Michalovich, D; Simpson, K D; Hessel, E M; Jutel, M; Martin-Fontecha, M; Palomares, O; Akdis, C A; O'Mahony, L

2017-11-01

Fatty acids and lipid mediator signaling play an important role in the pathogenesis of asthma, yet this area remains largely underexplored. The aims of this study were (i) to examine fatty acid levels and their metabolism in obese and nonobese asthma patients and (ii) to determine the functional effects of altered fatty acid metabolism in experimental models. Medium- and long-chain fatty acid levels were quantified in serum from 161 human volunteers by LC/MS. Changes in stearoyl-coenzyme A desaturase (SCD) expression and activity were evaluated in the ovalbumin (OVA) and house dust mite (HDM) murine models. Primary human bronchial epithelial cells from asthma patients and controls were evaluated for SCD expression and activity. The serum desaturation index (an indirect measure of SCD) was significantly reduced in nonobese asthma patients and in the OVA murine model. SCD1 gene expression was significantly reduced within the lungs following OVA or HDM challenge. Inhibition of SCD in mice promoted airway hyper-responsiveness. SCD1 expression was suppressed in bronchial epithelial cells from asthma patients. IL-4 and IL-13 reduced epithelial cell SCD1 expression. Inhibition of SCD reduced surfactant protein C expression and suppressed rhinovirus-induced IP-10 secretion, which was associated with increased viral titers. This is the first study to demonstrate decreased fatty acid desaturase activity in humans with asthma. Experimental models in mice and human epithelial cells suggest that inhibition of desaturase activity leads to airway hyper-responsiveness and reduced antiviral defense. SCD may represent a new target for therapeutic intervention in asthma patients. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

Schistosoma mansoni control in Cul de Sac Valley, Saint Lucia. II. Chemotherapy as a supplement to a focal mollusciciding programme.

Science.gov (United States)

Jordan, P; Cook, J A; Bartholomew, R K; Grist, E; Auguste, E

1980-01-01

After an intensive area-wide mollusciciding campaign, over four and a half years, transmission of Schistosoma mansoni was reduced. A cheaper scheme suitable for the follow-up or consolidation stage of control was evaluated and two selective population chemotherapy campaigns using hycanthone (2 mg/kg b.w.) and oxamniquine (15 mg/kg b.w.) were mounted. Prevalence dropped to 6% and 3% in areas with previously high and low levels of transmission respectively. Calculations suggested that these figures were falsely low and that perhaps 20% of the population were still excreting S. mansoni ova in small numbers. The unco-operative groups in the population are probably more important in maintaining a reservoir of infection in the community than persons with light infections undetected by the sedimentation concentration stool examination technique used. The benefit of more sensitive but more costly examination techniques is not clear since the importance of very light infections in transmission is uncertain. Case detection absorbs an increasing proportion of the total cost of chemotherapy programmes with fewer cases being found amongst the same number screened. Using hycanthone (649 treated) the cost per person protected was $0.74 and using oxamniquine (264 treated) $0.94. The need to develop low cost consolidation or follow-up procedures for preventing a resurgence of transmission after successful control, when the infection is no longer of public health importance, is stressed.

Schistosomiasis and HIV-1 infection in rural Zimbabwe

DEFF Research Database (Denmark)

Kallestrup, Per; Zinyama, Rutendo; Gomo, Exnevia

2005-01-01

Stunted development and reduced fecundity of Schistosoma parasites in immunodeficient mice and the impaired ability of human immunodeficiency virus 1 (HIV-1)-infected humans to excrete schistosome eggs have been described. This study explores the effect that HIV-1-associated immunodeficiency has...

Blood metabolome profiles of cattle colonized with Escherichia coli O157

Science.gov (United States)

Metabolomics is being increasingly used for diagnosis of asymptomatic/difficult-to-diagnose diseases in humans including parasitic (i.e. protozoan, schistosomal), viral (i.e. cytomegalovirus), bacterial (i.e. cystic fibrosis caused by Pseudomonas), genetic (i.e. autism) and cancer (i.e. gastric canc...

Effects of concentrated ambient particles on normal and hypersecretory airways in rats.

Science.gov (United States)

Harkema, Jack R; Keeler, Gerald; Wagner, James; Morishita, Masako; Timm, Edward; Hotchkiss, Jon; Marsik, Frank; Dvonch, Timothy; Kaminski, Norbert; Barr, Edward

2004-08-01

.5 from this local urban atmosphere. Rats in the inhalation studies were exposed for 1 day or for 4 or 5 consecutive days (10 hours/day) to either filtered air (controls) or concentrated ambient particles (CAPs) delivered by a Harvard ambient fine particle concentrator. Rats were killed 24 hours after the end of the exposure. Biochemical, morphometric, and molecular techniques were used to identify airway epithelial and inflammatory responses to CAPs. Lung lobes were also either intratracheally lavaged with saline to determine cellular composition and protein in bronchoalveolar lavage fluid (BALF) or removed for analysis by inductively coupled plasma-mass spectrometry (ICPMS) to detect retention of ambient PM2.5--derived trace elements. The Harvard concentrator effectively concentrated the fine ambient particles from this urban atmosphere (10-30 times) without significantly changing the major physicochemical features of the atmospheric particles. Daily CAPs mass concentrations during the 10-hour exposure period (0800-1800) in July ranged from 16 to 895 microg/m3 and in September ranged from 81 to 755 microg/m3. In general, chemical characteristics of ambient particles were conserved through the concentrator into the exposure chamber. Single or repeated exposures to CAPs did not cause adverse effects in the nasal or pulmonary airways of healthy F344 or BN rats. In addition, CAPs-related toxicity was not observed in F344 rats pretreated with bacterial endotoxin. Variable airway responses to CAPs exposure were observed in BN rats with preexisting allergic airway disease induced by OVA sensitization and challenge. Only OVA-challenged BN rats exposed to CAPs for 5 consecutive days in September 2000 had significant increases in airway mucosubstances and pulmonary inflammation compared to saline-challenged/air-exposed control rats. OVA-challenged BN rats that were repeatedly exposed to CAPs in July 2000 had only minor CAPs-related effects. In only the September 5-day exposure

Impact of old Schistosomiasis infection on the use of transient elastography (Fibroscan) for staging of fibrosis in chronic HCV patients.

Science.gov (United States)

Ramzy, Iman; Elsharkawy, Aisha; Fouad, Rabab; Hafez, Hanan Abdel; El Raziky, Maissa; El Akel, Wafaa; El-Sayed, Mohammad; Khattab, Hany; Shehata, Mohamed; Elsharkawy, Marwa; Radwan, Amr; Esmat, Gamal

2017-12-01

In tropical regions, Hepatitis C virus (HCV) - Schistosomiasis coinfection remains one of the health problems. With the new era of HCV treatment and the variety of methods of assessment of liver fibrosis so we aimed to evaluate the effectiveness of FibroScan for staging hepatic fibrosis in HCV-Schistosomiasis coinfected patients. Three groups of patients were enrolled. Group 1: chronic HCV with out antischistosomal antibody (122 patients), Group 2: chronic HCV with positive antischistosomal antibodies and without periportal tract thickening (122 patients), Group 3: chronic HCV with positive antischistosomal antibodies and ultrasonographic picture of periportal tract thickening (108 patients). Routine laboratory workup, serum Antischistosomal antibody, and Schistosomal antigen in serum were performed. Ultrasound guided liver biopsy with histopathological examination; abdominal ultrasound and fibroscan examination were done for all patients. The agreement between results of liver biopsy and results of fibroscan in the staging of fibrosis was the best in group 1 (55.7%), Although the agreement was higher among those with no periportal tract thickening (70.7%) and the disagreement was higher among those with positive schistosomal serology (66.5%), yet this relation was not statistically significant. Multivariate logistic regression analysis showed that disagreement is significantly associated with older age, higher BMI (≥30), and increase in anti Schistosomal antibody titer. Fibroscan is a reliable, non-invasive tool for staging hepatic fibrosis among HCV-schistosomiasis co-infected patients with no effect of the induced periportal tract thickening on the readings. Only higher antischistosomal antibody titres may cause disagreement between liver biopsy and fibroscan. Copyright © 2017 Elsevier B.V. All rights reserved.

Pharmacological manipulation of the chronic granulomatous reactions in the livers of mice infected with schistosomiasis.

Science.gov (United States)

Rainsford, K D

1985-01-01

The severe granulomatous reactions in the liver which occur following infestation by adult Schistosoma mansonii are largely initiated by invading eosinophils and monocytes. The present studies were designed to investigate the possibility that (a) anti-inflammatory drugs could be employed beneficially to attenuate the liver granulomatous reactions in schistosomiasis, and (b) that part of the therapeutic effects of anti-schistosomal (AS) drugs might be due to possible influences on arachidonate metabolism. Therefore the effects were determined of (a) AS as compared with NSAI drugs on eicosanoid metabolism in isolated human peripheral leucocyte populations, and (b) electron-microscopic changes in the livers of mice infected with Schistosoma mansoni in response to AS and/or NSAI drugs. Of the AS drugs only praziquantel (10-100 microM) inhibited 5-HETE production by the 5-lipoxygenase pathway. No effects were observed of this or the other AS drugs on prostaglandin production. In S. mansoni infected mice, praziquantel (250 mg/kg/d), given orally with indomethacin (5 mg/kg/d) for 5 days did not improve the inflammatory reactions around worms or eggs of schistosomes. Furthermore, both indomethacin (5 mg/kg/d) alone and benoxaprofen (20 mg/kg/d for 5 days) elicited liver changes suggestive of specific liver damage by these drugs. These results suggest that liver pathology may be enhanced by NSAI drugs perhaps as a consequence of the liver metabolism of these drugs being compromised. Their use to modify inflammatory reactions at the peak of liver schistosome infections may thus be contraindicated.

Co-administration of cholera toxin and apple polyphenol extract as a novel and safe mucosal adjuvant strategy.

Science.gov (United States)

Yoshino, Naoto; Fujihashi, Kohtaro; Hagiwara, Yukari; Kanno, Hiroyuki; Takahashi, Kiyomi; Kobayashi, Ryoki; Inaba, Noriyuki; Noda, Masatoshi; Sato, Shigehiro

2009-07-30

Although native cholera toxin (CT) is an extremely effective adjuvant, its toxicity prevents its use in humans. We report here that apple polyphenol extract (APE), obtained from unripe apples, reduces CT-induced morphological changes and cAMP accumulation. Based upon this finding, we have attempted to design a novel, effective and safe mucosal vaccine by using CT with several dosages of APE as nasal adjuvants. Mice nasally immunized with OVA plus CT and an optimal dosage of APE showed significantly reduced levels of inflammatory responses as well as total and OVA-specific IgE antibodies when compared with mice given without APE. However, levels of both mucosal and systemic OVA-specific antibody responses were maintained. Further, APE significantly down-regulated accumulation of CT in the olfactory nerves and epithelium. In summary, an optimal dosage of APE would take full advantage of mucosal adjuvanticity of native CT without any toxicity for application in humans.

Up-regulation of T lymphocyte and antibody production by inflammatory cytokines released by macrophage exposure to multi-walled carbon nanotubes

Energy Technology Data Exchange (ETDEWEB)

Grecco, Ana Carolina P; Mizutani, Erica; Peterlevitz, Alfredo C; Ceragioli, Helder J; Baranauskas, Vitor [Faculdade de Engenharia Eletrica e Computacao, Universidade de Campinas, Campinas, SP (Brazil); Paula, Rosemeire F O; Sartorelli, Juliana C; Milani, Ana M; Longhini, Ana Leda F; Oliveira, Elaine C; Pradella, Fernando; Silva, Vania D R; Moraes, Adriel S; Farias, Alessandro S; Santos, Leonilda M B, E-mail: leonilda@unicamp.br [Laboratorio de Neuroimunologia, Departamento Genetica, Evolucao e Bioagentes, Instituto de Biologia, Universidade de Campinas, Campinas, SP (Brazil)

2011-07-01

Our data demonstrate that multi-walled carbon nanotubes (MWCNTs) are internalized by macrophages, subsequently activating them to produce interleukin (IL)-12 (IL-12). This cytokine induced the proliferative response of T lymphocytes to a nonspecific mitogen and to ovalbumin (OVA). This increase in the proliferative response was accompanied by an increase in the expression of pro-inflammatory cytokines, such as interferon-gamma (IFN{gamma}), tumor necrosis factor-alpha (TNF{alpha}) and IL-6, in mice inoculated with MWCNTs, whether or not they had been immunized with OVA. A decrease in the expression of transforming growth factor-beta (TGF{beta}) was observed in the mice treated with MWCNTs, whereas the suppression of the expression of both TGF{beta} and IL-10 was observed in mice that had been both treated and immunized. The activation of the T lymphocyte response by the pro-inflammatory cytokines leads to an increase in antibody production to OVA, suggesting the important immunostimulatory effect of carbon nanotubes.

Up-regulation of T lymphocyte and antibody production by inflammatory cytokines released by macrophage exposure to multi-walled carbon nanotubes

Science.gov (United States)

Grecco, Ana Carolina P.; Paula, Rosemeire F. O.; Mizutani, Erica; Sartorelli, Juliana C.; Milani, Ana M.; Longhini, Ana Leda F.; Oliveira, Elaine C.; Pradella, Fernando; Silva, Vania D. R.; Moraes, Adriel S.; Peterlevitz, Alfredo C.; Farias, Alessandro S.; Ceragioli, Helder J.; Santos, Leonilda M. B.; Baranauskas, Vitor

2011-07-01

Our data demonstrate that multi-walled carbon nanotubes (MWCNTs) are internalized by macrophages, subsequently activating them to produce interleukin (IL)-12 (IL-12). This cytokine induced the proliferative response of T lymphocytes to a nonspecific mitogen and to ovalbumin (OVA). This increase in the proliferative response was accompanied by an increase in the expression of pro-inflammatory cytokines, such as interferon-gamma (IFNγ), tumor necrosis factor-alpha (TNFα) and IL-6, in mice inoculated with MWCNTs, whether or not they had been immunized with OVA. A decrease in the expression of transforming growth factor-beta (TGFβ) was observed in the mice treated with MWCNTs, whereas the suppression of the expression of both TGFβ and IL-10 was observed in mice that had been both treated and immunized. The activation of the T lymphocyte response by the pro-inflammatory cytokines leads to an increase in antibody production to OVA, suggesting the important immunostimulatory effect of carbon nanotubes.

Deep-Sea-Derived Butyrolactone I Suppresses Ovalbumin-Induced Anaphylaxis by Regulating Mast Cell Function in a Murine Model.

Science.gov (United States)

Liu, Qing-Mei; Xie, Chun-Lan; Gao, Yuan-Yuan; Liu, Bo; Lin, Wei-Xiang; Liu, Hong; Cao, Min-Jie; Su, Wen-Jin; Yang, Xian-Wen; Liu, Guang-Ming

2018-05-22

Deep-sea-derived butyrolactone I (BTL-I), which was identified as a type of butanolide, was isolated from Aspergillus sp. Ovalbumin (OVA)-induced BALB/c anaphylaxis was established to explore the antifood allergic activity of BTL-I. As a result, BTL-I was able to alleviate OVA-induced allergy symptoms, reduce the levels of histamine and mouse mast cell proteinases, inhibit OVA-specific IgE, and decrease the population of mast cells in the spleen and mesenteric lymph nodes. BTL-I also significantly suppressed mast-dependent passive cutaneous anaphylaxis. Additionally, the maturation of bone marrow-derived mast cells (BMMCs) declined as BTL-I caused down-regulation of c-KIT receptors. Furthermore, molecular docking analyses revealed that BTL-I interacted with the inhibitory receptor, FcγRIIB. In conclusion, the reduction of mast cell function by deep-sea-derived BTL-I as well as its interactions with the inhibitory receptor, FcγRIIB, may contribute to BTL-I-related protection against food anaphylaxis.

Avian Schistosomes and Outbreaks of Cercarial Dermatitis

Czech Academy of Sciences Publication Activity Database

Horák, P.; Mikeš, L.; Lichtenbergová, L.; Skála, V.; Soldánová, Miroslava; Brant, S. V.

2015-01-01

Roč. 28, č. 1 (2015), s. 165-190 ISSN 0893-8512 Institutional support: RVO:60077344 Keywords : fresh water snails * Lymnae stagnalis hemocytes * Trichobilharzia regenti schistosomatidae Subject RIV: FN - Epidemiology, Contagious Diseases ; Clinical Immunology Impact factor: 16.187, year: 2015

1 MS 079-06 Badmos

African Journals Online (AJOL)

Damary

2006-10-10

Oct 10, 2006 ... Background: Schistosomiasis is a chronic granulomatous inflammation that affects many systems in the body including the gastrointestinal tract. This study was carried out by reviewing all cases of schistosomal appendicitis, and documents any association with acute appendicitis. Objective: To review all ...

Glycomic Analysis of Life Stages of the Human Parasite Schistosoma mansoni Reveals Developmental Expression Profiles of Functional and Antigenic Glycan Motifs

NARCIS (Netherlands)

Smit, C.H.; van Diepen, A.; Nguyen, D.L.; Wuhrer, M.; Hoffmann, K.F.; Deelder, A.M.; Hokke, C.H.

2015-01-01

Glycans present on glycoproteins and glycolipids of the major human parasite Schistosoma mansoni induce innate as well as adaptive immune responses in the host. To be able to study the molecular characteristics of schistosome infections it is therefore required to determine the expression profiles

The role of snail aestivation in transmission of schistosomiasis in ...

African Journals Online (AJOL)

Aestivation therefore plays an important role in maintaining the transmission of schistosomiasis. This review assesses the possible impacts of climate change on the temporal and spatial distribution of schistosomiasis-transmitting snails with special emphasis on aestivation, and discusses the effect of schistosome infection ...

Variabilité de la compatibilité entre Schistosoma Haematobium et ...

African Journals Online (AJOL)

SARAH

30 janv. 2015 ... Homopatric and allopatric combinations were performed. The snail-schistosome compatibility and epidemiological involvement were assessed by the success rate of infestation (SRI). In total 2638 Bulinus truncatus and 778 B. globosus were infested. Three variants of S. haematobium subservient to their ...

Eosinophil granule proteins ECP and EPX as markers for a potential early-stage inflammatory lesion in female genital schistosomiasis (FGS)

DEFF Research Database (Denmark)

Ramarokoto, Charles Emile; Kildemoes, Anna M. O.; Randrianasolo, Bodo Sahondra

2014-01-01

pathology, as viable schistosome egg granulomas often are eosinophil rich. Here it was investigated whether eosinophil granule proteins ECP (eosinophil cationic protein) and EPX (eosinophil protein-X) in urine and genital lavage can be used as markers for active FGS lesions. METHODS: Uro-genital samples...

A Randomised, Double-blind, Placebo-controlled Trial of Trichuris suis ova in Active Crohn's Disease

DEFF Research Database (Denmark)

Schölmerich, Jürgen; Fellermann, Klaus; Seibold, Frank W

2017-01-01

Background and Aims: To investigate the efficacy and safety of three different dosages of embryonated, viable eggs of Trichuris suis [TSO] versus placebo for induction of remission in mildly-to-moderately active ileocolonic, uncomplicated Crohn's disease [CD]. Methods: Adults with active CD [n.......2%, and 47.2% of TSO 250, TSO 2500, and TSO 7500 patients, respectively, and in 42.9% of placebo recipients. TSO induced a dose-dependent immunological response. There was no response regarding laboratory markers of inflammation. Other secondary efficacy variables also showed no advantage of TSO over placebo...... for treatment of active CD. Administration of TSO did not result in any serious adverse drug reaction. Review of non-serious suspected adverse drug reactions following TSO did not reveal any safety concerns. Conclusions: Administration of 250-7500 TSO fortnightly over 12 weeks was safe and showed a dose...

Schistosoma mansoni : structural and biophysical aspects of Lewis X-antibody interactions

NARCIS (Netherlands)

Roon, Anne-Marie van

2005-01-01

Schistosomiasis (Bilharzia) is a tropical parasitic disease caused by schistosomes. At present more than 200 million people are infected by these parasites. If the infection is left untreated, the parasites can survive within the body for 5 years or more. The parasite has developed r escape

case report endomyocardial fibrosis associated with schistosoma

African Journals Online (AJOL)

2014-12-01

Dec 1, 2014 ... stored in containers and subsequently used for bathing. Both patients were ... His urine was amber and of adequate vol- ume. He had been ... schistosome specific antibody test for Schistosoma haematobium ... health problem, with the highest prevalence seen in communities ... newer drug targets.13,14.

An unexpected antibody response to an engineered influenza virus modifies CD8+ T cell responses.

Science.gov (United States)

Thomas, Paul G; Brown, Scott A; Yue, Wen; So, Jenny; Webby, Richard J; Doherty, Peter C

2006-02-21

The ovalbumin(323-339) peptide that binds H2I-A(b) was engineered into the globular heads of hemagglutinin (H) molecules from serologically non-cross-reactive H1N1 and H3N2 influenza A viruses, the aim being to analyze recall CD4+ T cell responses in a virus-induced respiratory disease. Prime/challenge experiments with these H1ova and H3ova viruses in H2(b) mice gave the predicted, ovalbumin-specific CD4+ T cell response but showed an unexpectedly enhanced, early expansion of viral epitope-specific CD8+ T cells in spleen and a greatly diminished inflammatory process in the virus-infected respiratory tract. At the same time, the primary antibody response to the H3N2 challenge virus was significantly reduced, an effect that has been associated with preexisting neutralizing antibody in other experimental systems. Analysis of serum from the H1ova-primed mice showed low-level binding to H3ova but not to the wild-type H3N2 virus. Experiments with CD4+ T cell-depleted and Ig-/- mice indicated that this cross-reactive Ig is indeed responsible for the modified pathogenesis after respiratory challenge. Furthermore, the effect does not seem to be virus-dose related, although it does require infection. These findings suggest intriguing possibilities for vaccination and, at the same time, emphasize that engineered modifications in viruses may have unintended immunological consequences.

DermAll nanomedicine for allergen-specific immunotherapy.

Science.gov (United States)

Garaczi, Edina; Szabó, Kornélia; Francziszti, László; Csiszovszki, Zsolt; Lőrincz, Orsolya; Tőke, Enikő R; Molnár, Levente; Bitai, Tamás; Jánossy, Tamás; Bata-Csörgő, Zsuzsanna; Kemény, Lajos; Lisziewicz, Julianna

2013-11-01

Allergen-specific immunotherapy (ASIT) the only disease-modifying treatment for IgE-mediated allergies is characterized with long treatment duration and high risk of side effects. We investigated the safety, immunogenicity and efficacy of a novel ASIT, called DermAll, in an experimental allergic rhinitis model. We designed and characterized DermAll-OVA, a synthetic plasmid pDNA/PEIm nanomedicine expressing ovalbumin (OVA) as model allergen. DermAll-OVA was administered topically with DermaPrep device to target Langerhans cells. To detect the clinical efficacy of DermAll ASIT we quantified the nasal symptoms and characterized the immunomodulatory activity of DermAll ASIT by measuring cytokine secretion after OVA-stimulation of splenocytes and antibodies from the sera. In allergic mice DermAll ASIT was as safe as Placebo, balanced the allergen-induced pathogenic TH2-polarized immune responses, and decreased the clinical symptoms by 52% [32%, 70%] compared to Placebo. These studies suggest that DermAll ASIT is safe and should significantly improve the immunopathology and symptoms of allergic diseases. A novel allergen-specific immunotherapy for IgE-mediated allergies is presented in this paper, using an experimental allergic rhinitis model and a synthetic plasmid pDNA/PEIm nanomedicine expressing ovalbumin as model allergen. Over 50% reduction of symptoms was found as the immune system's balance was favorably altered toward more TH2-polarized immune responses. Copyright © 2013 Elsevier Inc. All rights reserved.

Immunomodulatory effect of tea saponin in immune T-cells and T-lymphoma cells via regulation of Th1, Th2 immune response and MAPK/ERK2 signaling pathway.

Science.gov (United States)

Bhardwaj, Jyoti; Chaudhary, Narendra; Seo, Hyo-Jin; Kim, Min-Yong; Shin, Tai-Sun; Kim, Jong-Deog

2014-06-01

The anti-cancer activity of saponins and phenolic compounds present in green tea was previously reported. However, the immunomodulatory and adjuvanticity activity of tea saponin has never been studied. In this study, we investigated the immunomodulatory effect of tea saponin in T-lymphocytes and EL4 cells via regulation of cytokine response and mitogen-activated protein kinases (MAPK) signaling pathway. Quantitative analysis of mRNA expression level of cytokines were performed by reverse transcription polymerase chain reaction following stimulation with tea saponin, ovalbumin (OVA) alone or tea saponin in combination with OVA. Tea saponin inhibited the proliferation of EL4 cells measured in a dose-dependent manner. No cytotoxicity effect of tea saponin was detected in T-lymphocytes; rather, tea saponin enhanced the proliferation of T-lymphocytes. Tea saponin with OVA increased the expression of interleukin (IL)-1, IL-2, IL-12, interferon-γ and tumor necrosis factor (TNF)-α and decreased the expression level of IL-10 and IL-8 in T-lymphocytes. Furthermore, tea saponin, in the presence of OVA, downregulated the MAPK signaling pathway via inhibition of IL-4, IL-8 and nuclear factor kappaB (NF-κB) in EL4 cells. Th1 cytokines enhancer and Th2 cytokines and NF-κB inhibitor, tea saponin can markedly inhibit the proliferation and invasiveness of T-lymphoma (EL4) cells, possibly due to TNF-α- and NF-κB-mediated regulation of MAPK signaling pathway.

Parasites in Forensic Science: a historic perspective

Science.gov (United States)

Cardoso, Rita; Alves, Helena; Richter, Joachim; Botelho, Monica C

Parasites show a great potential to Forensic Science. Forensic Science is the application of any science and methodology to the legal system. The forensic scientist collects and analyses the physical evidence and produce a report of the results to the court. A parasite is an organism that lives at the expense of another and they exist in any ecosystem. Parasites are the cause of many important diseases. The forensic scientists can use the parasites to identify a crime scene, to determine the murder weapon or simply identify an individual. The applications for parasites in the Forensic Science can be many and more studies should be made in Forensic Parasitology. The most important parasites in Forensic Science are helminths specifically schistosomes. Through history there are many cases where schistosomes were described in autopsies and it was related to the cause of death. Here we review the applications of parasites in Forensic Science and its importance to the forensic scientist.

Protein acetylation sites mediated by Schistosoma mansoni GCN5

International Nuclear Information System (INIS)

Moraes Maciel, Renata de; Furtado Madeiro da Costa, Rodrigo; Meirelles Bastosde Oliveira, Francisco; Rumjanek, Franklin David; Fantappie, Marcelo Rosado

2008-01-01

The transcriptional co-activator GCN5, a histone acetyltransferase (HAT), is part of large multimeric complexes that are required for chromatin remodeling and transcription activation. As in other eukaryotes, the DNA from the parasite Schistosome mansoni is organized into nucleosomes and the genome encodes components of chromatin-remodeling complexes. Using a series of synthetic peptides we determined that Lys-14 of histone H3 was acetylated by the recombinant SmGCN5-HAT domain. SmGCN5 was also able to acetylate schistosome non-histone proteins, such as the nuclear receptors SmRXR1 and SmNR1, and the co-activator SmNCoA-62. Electron microscopy revealed the presence of SmGCN5 protein in the nuclei of vitelline cells. Within the nucleus, SmGCN5 was found to be located in interchromatin granule clusters (IGCs), which are transcriptionally active structures. The data suggest that SmGCN5 is involved in transcription activation

Schistosoma mansoni: parasitology and immunology of baboons vaccinated with irradiated cryopreserved schistosomula

Energy Technology Data Exchange (ETDEWEB)

Damian, R T; Powell, M R; Roberts, M L [Georgia Univ., Athens (USA). Dept. of Zoology; Clark, J D [Georgia Univ., Athens (USA). Lab. Animal Medicine; Stirewalt, M A; Lewis, F A [Biomedical Research Inst., Rockville, MD (USA)

1985-06-01

Young baboons (Papio cynocephalus) were vaccinated with ..gamma..-irradiated (500 Gy) cryopreserved Puerto Rican strain schistosomula of S. mansoni. Protection against heterologous, normal Kenyan Strain S. mansoni challenge infection was erratic and partial; and two putative correlates of immunity, reduced worm fecundity and change in worm location (anterior shift) were not observed. However, immunization of baboons with this vaccine resulted in a stimulated immune system. Both cellular and humoral anamnesis were demonstrable in vaccinated-challenged baboons. Schistosome infection-associated IgM hypergammaglobulinemia was also greatly reduced in vaccinated-challenged baboons. However IgG antibodies to adult, egg, and cercarial antigens were increased after challenge infection in preimmunized baboons. Vaccination appears to have resulted in a redirection of the immune system into anti-parasite channels, but this more specific immune response was insufficient to confer good protection against challenge infection in this experiment. The dampening effect of the vaccine on the hypergammaglobulinemia of schistosomiasis is another candidate for a possible ''anti-pathogenesis'' effect of irradiated schistosome larval vaccines.

Embryo developmental events and the egg case of the Aleutian skate Bathyraja aleutica (Gilbert) and the Alaska skate Bathyraja parmifera (Bean).

Science.gov (United States)

Hoff, G R

2009-02-01

Embryo development events were correlated with egg-case changes for the Aleutian skate Bathyraja aleutica and the Alaska skate Bathyraja parmifera. Yolk absorption underwent two phases: that of steady absorption during early development and that of rapid yolk absorption during the final development stages. Total length (L(T)) for 50% of the pre-hatching embryos egg-case jelly disappearance was 92.04 mm (range 81-102 mm) and 99.36 mm (range 81-100 mm) for B. aleutica and B. parmifera, respectively, allowing the inner chamber to open to seawater flow. The tail filament underwent three phases of growth: rapid elongation during early development (70 mm L(T) for both species and the sex ratio was 1:1 well before hatching. Egg cases that were devoid of an ova or developing embryo were c. 5.0 and 6.5% of the egg cases examined for B. aleutica and B. parmifera, respectively. Measurements showed that egg cases containing only egg jelly were smaller in both width and length than those possessing an ova. Embryo stages were punctuated with distinct events that correlated with egg case changes controlling the internal environment of the developing embryo.

Cancer associated aberrant protein o-glycosylation can modify antigen processing and immune response

DEFF Research Database (Denmark)

Madsen, Caroline B; Petersen, Cecilie; Lavrsen, Kirstine

2012-01-01

Aberrant glycosylation of mucins and other extracellular proteins is an important event in carcinogenesis and the resulting cancer associated glycans have been suggested as targets in cancer immunotherapy. We assessed the role of O-linked GalNAc glycosylation on antigen uptake, processing......, and presentation on MHC class I and II molecules. The effect of GalNAc O-glycosylation was monitored with a model system based on ovalbumin (OVA)-MUC1 fusion peptides (+/- glycosylation) loaded onto dendritic cells co-cultured with IL-2 secreting OVA peptide-specific T cell hybridomas. To evaluate the in vivo...

Projecting the long-term impact of school- or community-based mass-treatment interventions for control of Schistosoma infection.

Directory of Open Access Journals (Sweden)

Xiaoxia Wang

Full Text Available Schistosomiasis remains a significant health burden in many areas of the world. Morbidity control, focused on limiting infection intensity through periodic delivery of anti-schistosomal medicines, is the thrust of current World Health Organization guidelines (2006 for reduction of Schistosoma-related disease. A new appreciation of the lifetime impact of repeated Schistosoma infection has directed attention toward strategies for greater suppression of parasite infection per se, with the goal of transmission interruption. Variations in drug schedules involving increased population coverage and/or treatment frequency are now undergoing field trials. However, their relative effectiveness in long-term infection suppression is presently unknown.Our study used available field data to calibrate advanced network models of village-level Schistosoma transmission to project outcomes of six different community- or school age-based programs, as compared to the impact of current 2006 W.H.O. recommended control strategies. We then scored the number of years each of 10 typical villages would remain below 10% infection prevalence (a practicable level associated with minimal prevalence of disease. All strategies that included four annual treatments effectively reduced community prevalence to less than 10%, while programs having yearly gaps ('holidays' failed to reach this objective in half of the communities. Effective post-program suppression of infection prevalence persisted in half of the 10 villages for 7-10 years, whereas in five high-risk villages, program effects on prevalence lasted zero to four years only.At typical levels of treatment adherence (60 to 70%, current WHO recommendations will likely not achieve effective suppression of Schistosoma prevalence unless implemented for ≥6 years. Following more aggressive 4 year annual intervention, some communities may be able to continue without further intervention for 8-10 years, while in higher

[Cloning and expressing of cyclophilin B gene from Schistosoma japonnicum and the analysis of immunoprotective effect].

Science.gov (United States)

Peng, Jinbiao; Han, Hongxiao; Hong, Yang; Wang, Yan; Guo, Fanji; Shi, Yaojun; Fu, Zhiqiang; Liu, Jinming; Cheng, Guofeng; Lin, Jiaojiao

2010-03-01

The present study was intend to clone and express the cDNA encoding Cyclophilin B (CyPB) of Schistosoma japonicum, its preliminary biological function and further immunoprotective effect against schistosome infection in mice. RT-PCR technique was applied to amplify a full-length cDNA encoding protein Cyclophilin B (Sj CyPB) from schistosomula cDNA. The expression profiles of Sj CyPB were determined by Real-time PCR using the template cDNAs isolated from 7, 13, 18, 23, 32 and 42 days parasites. The cDNA containing the Open Reading Frame of CyPB was then subcloned into a pGEX-6P-1 vector and transformed into competent Escherichia coli BL21 for expressing. The recombinant protein was renaturated, purified and its antigenicity were detected by Western blotting, and the immunoprotective effect induced by recombinant Sj CyPB was evaluated in Balb/C mice. The cDNA containing the ORF of Sj CyPB was cloned with the length of 672 base pairs, encoding 223 amino acids. Real-time PCR analysis revealed that the gene had the highest expression in 18-day schistosomula, suggesting that Sj CyPB was schistosomula differentially expressed gene. The recombinant protein showed a good antigenicity detected by Western blotting. Animal experiment indicated that the vaccination of recombinant CyPB protein in mice led to 31.5% worm and 41.01% liver egg burden reduction, respectively, compared with those of the control. A full-length cDNA differentially expressed in schistosomula was obtained. The recombinant Sj CyPB protein could induce partial protection against schistosome infection.

Ursodeoxycholic acid suppresses eosinophilic airway inflammation by inhibiting the function of dendritic cells through the nuclear farnesoid X receptor.

Science.gov (United States)

Willart, M A M; van Nimwegen, M; Grefhorst, A; Hammad, H; Moons, L; Hoogsteden, H C; Lambrecht, B N; Kleinjan, A

2012-12-01

Ursodeoxycholic acid (UDCA) is the only known beneficial bile acid with immunomodulatory properties. Ursodeoxycholic acid prevents eosinophilic degranulation and reduces eosinophil counts in primary biliary cirrhosis. It is unknown whether UDCA would also modulate eosinophilic inflammation outside the gastrointestinal (GI) tract, such as eosinophilic airway inflammation seen in asthma. The working mechanism for its immunomodulatory effect is unknown. The immunosuppressive features of UDCA were studied in vivo, in mice, in an ovalbumin (OVA)-driven eosinophilic airway inflammation model. To study the mechanism of action of UDCA, we analyzed the effect of UDCA on eosinophils, T cells, and dendritic cell (DCs). DC function was studied in greater detail, focussing on migration and T-cell stimulatory strength in vivo and interaction with T cells in vitro as measured by time-lapse image analysis. Finally, we studied the capacity of UDCA to influence DC/T cell interaction. Ursodeoxycholic acid treatment of OVA-sensitized mice prior to OVA aerosol challenge significantly reduced eosinophilic airway inflammation compared with control animals. DCs expressed the farnesoid X receptor for UDCA. Ursodeoxycholic acid strongly promoted interleukin (IL)-12 production and enhanced the migration in DCs. The time of interaction between DCs and T cells was sharply reduced in vitro by UDCA treatment of the DCs resulting in a remarkable T-cell cytokine production. Ursodeoxycholic acid-treated DCs have less capacity than saline-treated DCs to induce eosinophilic inflammation in vivo in Balb/c mice. Ursodeoxycholic acid has the potency to suppress eosinophilic inflammation outside the GI tract. This potential comprises to alter critical function of DCs, in essence, the effect of UDCA on DCs through the modulation of the DC/T cell interaction. © 2012 John Wiley & Sons A/S.

Virally inactivated human platelet concentrate lysate induces regulatory T cells and immunosuppressive effect in a murine asthma model.

Science.gov (United States)

Lee, Yueh-Lun; Lee, Lin-Wen; Su, Chen-Yao; Hsiao, George; Yang, Yi-Yuan; Leu, Sy-Jye; Shieh, Ying-Hua; Burnouf, Thierry

2013-09-01

Platelet concentrate lysates (PCLs) are increasingly used in regenerative medicine. We have developed a solvent/detergent (S/D)-treated PCL. The functional properties of this preparation should be unveiled. We hypothesized that, due to transforming growth factor-β1 (TGF-β1) content, PCLs may exert immunosuppressive and anti-inflammatory functions. PCL was prepared by S/D treatment, oil extraction, and hydrophobic interaction chromatography. The content of TGF-β in PCL was determined by enzyme-linked immunosorbent assay. Cultured CD4+ T cells were used to investigate the effects of PCL on expression of transcription factor forkhead box P3 (Foxp3), the inhibition of T-cell proliferation, and cytokine production. The regulatory function of PCL-converted CD4+ T cells was analyzed by suppressive assay. The BALB/c mice were given PCL-converted CD4+ T cells before ovalbumin (OVA) sensitization and challenge using an asthma model. Inflammatory parameters, such as the level of immunoglobulin E (IgE), airway hyperresponsiveness (AHR), bronchial lavage fluid eosinophils, and cytokines were assayed. Recombinant human (rHu) TGF-β1 was used as control. PCL significantly enhanced the development of CD4+Foxp3+-induced regulatory T cells (iTregs). Converted iTregs produced neither Th1 nor Th2 cytokines and inhibited normal T-cell proliferation. PCL- and rHuTGF-β-converted CD4+ T cells prevented OVA-induced asthma. PCL- and rHuTGF-β-modified T cells both significantly reduced expression levels of OVA-specific IgE and significantly inhibited the development of AHR, airway eosinophilia, and Th2 responses in mice. S/D-treated PCL promotes Foxp3+ iTregs and exerts immunosuppressive and anti-inflammatory properties. This finding may help to understand the clinical properties of platelet lysates. © 2013 American Association of Blood Banks.

Oral Administration of Recombinant Saccharomyces boulardii Expressing Ovalbumin-CPE Fusion Protein Induces Antibody Response in Mice.

Science.gov (United States)

Bagherpour, Ghasem; Ghasemi, Hosnie; Zand, Bahare; Zarei, Najmeh; Roohvand, Farzin; Ardakani, Esmat M; Azizi, Mohammad; Khalaj, Vahid

2018-01-01

Saccharomyces boulardii , a subspecies of Saccharomyces cerevisiae , is a well-known eukaryotic probiotic with many benefits for human health. In the present study, a recombinant strain of S. boulardii was prepared to use as a potential oral vaccine delivery vehicle. In this sense, a ura3 auxotroph strain of S. boulardii CNCM I-745 (known as S. cerevisiae HANSEN CBS 5926, Yomogi ® ) was generated using CRISPR/Cas9 methodology. Then a gene construct encoding a highly immunogenic protein, ovalbumin (OVA), was prepared and transformed into the ura3 - S. boulardii . To facilitate the transport of the recombinant immunogen across the intestinal barrier, a claudin-targeting sequence from Clostridium perfringens enterotoxin (CPE) was added to the C-terminus of the expression cassette. The recombinant S. boulardii strain expressing the OVA-CPE fusion protein was then administered orally to a group of mice, and serum IgG and fecal IgA levels were evaluated by ELISA. Our results demonstrated that anti-OVA IgG in serum significantly increased in test group ( P boulardii or PBS), and the fecal IgA titer was significantly higher in test group ( P boulardii strain expressing the similar construct lacking C-terminal CPE was also administered orally. The result showed an increased level of serum IgG in group receiving yeasts expressing the CPE negative construct compared to control groups; however, the fecal IgA levels did not increase significantly. In conclusion, our findings indicated that the yeast S. boulardii , as a delivery vehicle with possible immunomodulatory effects, and c-CPE, as a targeting tag, synergistically assist to stimulate systemic and local immunity. This proposed recombinant S. boulardii system might be useful in the expression of other antigenic peptides, making it as a promising tool for oral delivery of vaccines or therapeutic proteins.

Montelukast treatment (cysteinyl leukotriene receptor antagonist in a model of food allergy: modifications in lymphatic cell population from rectal mucosa Tratamiento con Montelukast (antagonista cisteinílico del receptor de leucotrienos en un modelo de alergia alimentaria: cambios en la población linfocítica de la mucosa renal

Directory of Open Access Journals (Sweden)

M. Vinuesa

2010-07-01

Full Text Available Objective: the aim is to determine immunopathological modifications in rectal mucosa from rabbits after local challenge in ovalbumin (OVA sensitized animals previously treated with montelukast. Material and methods: experimental design: thirty two rabbits divided into four groups: G1: normal; G2: subcutaneously OVA sensitized; G3: sensitized, locally OVA challenged and sampled 4 hours after challenge; and G4: sensitized, locally OVA challenged and treated 4 hours before challenge with montelukast (0.15 mg/kg. Specific anti-OVA IgE levels were evaluated by passive cutaneous anaphylaxis test (PCA. In each group 200 high microscopical power fields (HPF were counted. Results were expressed as arithmetic mean and SE. Anti -CD4, CD5, µ chain monoclonal antibodies were used. Avidin biotin horseradish peroxidase system was used. Results: CD 4: G1: 8.3 ± 0.06; G2: 13.4 ± 0.08, G3: 8.25 ± 0.06, G4: 11.8 ± 0.02. CD 5: G1: 7.3 ± 0.05; G2: 9.4 ± 0.05, G3: 11.3 ± 0.06, G4: 8.1 ± 0.06. μ chain: G1: 10.4 ± 0.06; G2: 3.8 ± 0.02, G3: 6.0 ± 0.10, G4: 2.2 ± 0.10. In all cases, experimental groups (G3 vs. G4 presented statistical significant differences (p < 0.05. CD4+, CD5+ cells and μ chain+ decrease in experimental group (G4, probably due to lymphocyte migration inhibition to challenged mucosa. μ chain+ cell decrease could be based on B cell activation and expression of different surface immunoglobulins. Cells expressing μ chain decreased in G2 and G3 likely due to activation of B cells and subsequent expression of other immunoglobulin chains in cell surface. Conclusions: we conclude that obtained data are important to elucidate immunopathology of local anaphylactic reaction in rectal mucosa from systemic sensitized animals after treatment with montelukast.

Montelukast treatment (cysteinyl leukotriene receptor antagonist in a model of food allergy: modifications in lymphatic cell population from rectal mucosa

Directory of Open Access Journals (Sweden)

M. Vinuesa

Full Text Available Objective: the aim is to determine immunopathological modifications in rectal mucosa from rabbits after local challenge in ovalbumin (OVA sensitized animals previously treated with montelukast. Material and methods: experimental design: thirty two rabbits divided into four groups: G1: normal; G2: subcutaneously OVA sensitized; G3: sensitized, locally OVA challenged and sampled 4 hours after challenge; and G4: sensitized, locally OVA challenged and treated 4 hours before challenge with montelukast (0.15 mg/kg. Specific anti-OVA IgE levels were evaluated by passive cutaneous anaphylaxis test (PCA. In each group 200 high microscopical power fields (HPF were counted. Results were expressed as arithmetic mean and SE. Anti -CD4, CD5, µ chain monoclonal antibodies were used. Avidin biotin horseradish peroxidase system was used. Results: CD 4: G1: 8.3 ± 0.06; G2: 13.4 ± 0.08, G3: 8.25 ± 0.06, G4: 11.8 ± 0.02. CD 5: G1: 7.3 ± 0.05; G2: 9.4 ± 0.05, G3: 11.3 ± 0.06, G4: 8.1 ± 0.06. μ chain: G1: 10.4 ± 0.06; G2: 3.8 ± 0.02, G3: 6.0 ± 0.10, G4: 2.2 ± 0.10. In all cases, experimental groups (G3 vs. G4 presented statistical significant differences (p < 0.05. CD4+, CD5+ cells and μ chain+ decrease in experimental group (G4, probably due to lymphocyte migration inhibition to challenged mucosa. μ chain+ cell decrease could be based on B cell activation and expression of different surface immunoglobulins. Cells expressing μ chain decreased in G2 and G3 likely due to activation of B cells and subsequent expression of other immunoglobulin chains in cell surface. Conclusions: we conclude that obtained data are important to elucidate immunopathology of local anaphylactic reaction in rectal mucosa from systemic sensitized animals after treatment with montelukast.

Clonorchis sinensis-derived total protein attenuates airway inflammation in murine asthma model by inducing regulatory T cells and modulating dendritic cell functions

Energy Technology Data Exchange (ETDEWEB)

Jeong, Young-Il [Div. of Malaria and Parasitic Diseases, Korea Centers for Disease Control and Prevention, Osong (Korea, Republic of); Kim, Seung Hyun [Div. of AIDS, National Institute of Health, Korea Centers for Disease Control and Prevention, Osong (Korea, Republic of); Ju, Jung Won; Cho, Shin Hyeong; Lee, Won Ja [Div. of Malaria and Parasitic Diseases, Korea Centers for Disease Control and Prevention, Osong (Korea, Republic of); Park, Jin Wook; Park, Yeong-Min [Dept. of Microbiology and Immunology, College of Medicine, Pusan National University, Yang-San (Korea, Republic of); Lee, Sang Eun, E-mail: ondalgl@cdc.go.kr [Div. of Malaria and Parasitic Diseases, Korea Centers for Disease Control and Prevention, Osong (Korea, Republic of)

2011-04-22

Highlights: {yields} Treatment with Clonorchis sinensis-derived total protein attenuates OVA-induced airway inflammation and AHR to methacholine. {yields} Induction of CD4{sup +}CD25{sup +}Foxp3{sup +} T cells and IL-10 along with suppression of splenocyte proliferation by C. sinensis-derived total protein. {yields} C. sinensis-derived total protein interferes with the expression of co-stimulatory molecules in DCs. -- Abstract: Asthma is characterized by Th2-mediated inflammation, resulting in airway hyperresponsiveness (AHR) through airway remodeling. Recent epidemiological and experimental reports have suggested an inverse relationship between the development of allergy and helminth infections. Infection by Clonorchis sinensis, a liver fluke that resides in the bile duct of humans, is endemic predominantly in Asia including Korea and China. Using a murine model for asthma, we investigated the effects of C. sinensis-derived total protein (Cs-TP) on allergen-induced airway inflammation and the mechanism underlying the protective effects of Cs-TP administration on asthma. Treatment with Cs-TP attenuated OVA-induced airway inflammation and methacholine-induced AHR, as well as eosinophilia development, lymphocyte infiltration into the lung, and goblet cell metaplasia. This protective effect of Cs-TP is associated with markedly reduced OVA-specific IgE and Th1/Th2 cytokine production. Moreover, Cs-TP increased the number of CD4{sup +}CD25{sup +}Foxp3{sup +} regulatory T (Treg) cells as well as their suppressive activity. In fact, proliferation of OVA-restimulated splenocytes was suppressed significantly. Cs-TP also inhibited the expression of such co-stimulatory molecules as CD80, CD86, and CD40 in LPS- or OVA-stimulated dendritic cells (DCs), suggesting that Cs-TP could interfere with the capacity of airway DCs to prime naive T cells. These data demonstrate the capacity of C. sinensis to ameliorate allergic asthma and broaden our understanding of the paradoxical

Prevalence of urinary Schistosomiasis in Umuowele, Agulu ...

African Journals Online (AJOL)

Fragment Length Polymorphism (PCR-RFLP) was used for snail species identification. Results: Haematuria revealed 48.1% prevalence rate among the pupils while PCR showed 58.3%. Three snails were also positive for schistosome infection one of which was identified as Bulinus truncatus while the other two belonged to ...

prevalence and intensity of single and mixed schistosoma mansoni ...

African Journals Online (AJOL)

2013-02-02

Feb 2, 2013 ... drugs for their treatment schistosome infections continue to exert significant morbidity in sub tropical ..... Classification of intensity of schistosomiasis among the study subjects: Majority of S. mansoni (75.8%) cases .... PLoS Negl Trop Dis. 2009;. 3, e379. 4. WHO.Preventive chemotherapy databank. World.

Therapeutic potential of anti-IL-1β IgY in guinea pigs with allergic asthma induced by ovalbumin.

Science.gov (United States)

Wei-xu, Hu; Qin, Xiang; Zhu, Wen; Yuan-yi, Chen; Li-feng, Zeng; Zhi-yong, Liu; Dan, He; Xiao-mu, Wu; Guo-zhu, Hu

2014-03-01

Interleukin-1 beta (IL-1β) plays pivotal roles in the progression of allergic airway inflammation. This study aims to determine whether the blockade of IL-1β can inhibit airway inflammation in guinea pigs with allergic asthma induced by the inhalation of aerosolized ovalbumin (OVA). Healthy guinea pigs treated with saline were used as normal controls (group C). The guinea pigs with allergic asthma induced by the inhalation of aerosolized OVA were randomly divided into three groups: (1) the M group containing negative control animals treated with saline; (2) the Z1 group containing animals treated by the inhalation of atomized 0.1% anti-IL-1β immunoglobulin yolk (IgY); and (3) the Z2 group containing positive control animals that were treated with budesonide. The inflammatory cells in the peripheral blood (PB) and bronchoalveolar lavage fluid (BALF) were evaluated using methylene blue and eosin staining. Cytokine concentrations were measured using an enzyme-linked immunosorbent assay. Pulmonary sections were examined using hematoxylin-eosin staining. Allergic inflammation and damage to the pulmonary tissues were decreased in the Z1 group compared to the M group. Eosinophils and neutrophils in the PB and BALF were significantly decreased in the Z1 group compared to the M group (Pguinea pigs with allergic asthma. The inhibitory activity may be due to the decrease in the numbers of eosinophils and neutrophils and the reduced levels of inflammatory cytokines and IgE in the PB and BALF. Copyright © 2013 Elsevier Ltd. All rights reserved.

Structural basis for the inhibition of histone deacetylase 8 (HDAC8, a key epigenetic player in the blood fluke Schistosoma mansoni.

Directory of Open Access Journals (Sweden)

Martin Marek

Full Text Available The treatment of schistosomiasis, a disease caused by blood flukes parasites of the Schistosoma genus, depends on the intensive use of a single drug, praziquantel, which increases the likelihood of the development of drug-resistant parasite strains and renders the search for new drugs a strategic priority. Currently, inhibitors of human epigenetic enzymes are actively investigated as novel anti-cancer drugs and have the potential to be used as new anti-parasitic agents. Here, we report that Schistosoma mansoni histone deacetylase 8 (smHDAC8, the most expressed class I HDAC isotype in this organism, is a functional acetyl-L-lysine deacetylase that plays an important role in parasite infectivity. The crystal structure of smHDAC8 shows that this enzyme adopts a canonical α/β HDAC fold, with specific solvent exposed loops corresponding to insertions in the schistosome HDAC8 sequence. Importantly, structures of smHDAC8 in complex with generic HDAC inhibitors revealed specific structural changes in the smHDAC8 active site that cannot be accommodated by human HDACs. Using a structure-based approach, we identified several small-molecule inhibitors that build on these specificities. These molecules exhibit an inhibitory effect on smHDAC8 but show reduced affinity for human HDACs. Crucially, we show that a newly identified smHDAC8 inhibitor has the capacity to induce apoptosis and mortality in schistosomes. Taken together, our biological and structural findings define the framework for the rational design of small-molecule inhibitors specifically interfering with schistosome epigenetic mechanisms, and further support an anti-parasitic epigenome targeting strategy to treat neglected diseases caused by eukaryotic pathogens.

A diagnostic dilemma of right lower lobe collapse caused by pulmonary bilharsiasis.

Science.gov (United States)

Sersar, Sameh Ibrahim; Abulmaaty, Reda Ahmed; Elnahas, Hala Ahmed; Moussa, Sherif Abdou; Shiha, Usama A; Ghafar, Wael A Abdel; Elmotawaly, Raed A

2006-02-01

A 32-year-old male was presented with massive haemoptysis. An urgent chest X-ray (Fig. 1a) and CT chest (Fig. 1b-e) was done revealing a right lower lobe consolidation collapse. An urgent rigid bronchoscopy was performed to localize the source of bleeding and try to control it. A right lower lobectomy was done using a double-lumen endotracheal tube. Preoperative and intraoperative impressions of non-specific inflammation were accused to be the aetiology. Histopathology revealed pulmonary venous congestion with bilharsial ova.

Distribution of Schistosomiasis and Soil Transmitted Helminthiasis in Zimbabwe: Towards a National Plan of Action for Control and Elimination

Science.gov (United States)

Midzi, Nicholas; Mduluza, Takafira; Chimbari, Moses J.; Tshuma, Clement; Charimari, Lincoln; Mhlanga, Gibson; Manangazira, Portia; Munyati, Shungu M.; Phiri, Isaac; Mutambu, Susan L.; Midzi, Stanley S.; Ncube, Anastancia; Muranzi, Lawrence P.; Rusakaniko, Simbarashe; Mutapi, Francisca

2014-01-01

Background Schistosomiasis and STH are among the list of neglected tropical diseases considered for control by the WHO. Although both diseases are endemic in Zimbabwe, no nationwide control interventions have been implemented. For this reason in 2009 the Zimbabwe Ministry of Health and Child Care included the two diseases in the 2009–2013 National Health Strategy highlighting the importance of understanding the distribution and burden of the diseases as a prerequisite for elimination interventions. It is against this background that a national survey was conducted. Methodology A countrywide cross-sectional survey was carried out in 280 primary schools in 68 districts between September 2010 and August 2011. Schistosoma haematobium was diagnosed using the urine filtration technique. Schistosoma mansoni and STH (hookworms, Trichuris trichiura, Ascaris lumbricoides) were diagnosed using both the Kato Katz and formol ether concentration techniques. Main findings Schistosomiasis was more prevalent country-wide (22.7%) than STH (5.5%). The prevalence of S. haematobium was 18.0% while that of S. mansoni was 7.2%. Hookworms were the most common STH with a prevalence of 3.2% followed by A. lumbricoides and T. trichiura with prevalence of 2.5% and 0.1%, respectively. The prevalence of heavy infection intensity as defined by WHO for any schistosome species was 5.8% (range 0%–18.3% in districts). Only light to moderate infection intensities were observed for STH species. The distribution of schistosomiasis and STH varied significantly between provinces, districts and schools (p<0.001). Overall, the prevalence of co-infection with schistosomiasis and STH was 1.5%. The actual co-endemicity of schistosomiasis and STH was observed in 43 (63.2%) of the 68 districts screened. Conclusion and recommendations This study provided comprehensive baseline data on the distribution of schistosomiasis and STH that formed the basis for initiating a national control and elimination programme

Arctigenin from Fructus Arctii (Seed of Burdock) Reinforces Intestinal Barrier Function in Caco-2 Cell Monolayers

Science.gov (United States)

Shin, Hee Soon; Jung, Sun Young; Back, Su Yeon; Do, Jeong-Ryong; Shon, Dong-Hwa

2015-01-01

Fructus Arctii is used as a traditional herbal medicine to treat inflammatory diseases in oriental countries. This study aimed to investigate effect of F. Arctii extract on intestinal barrier function in human intestinal epithelial Caco-2 cells and to reveal the active component of F. Arctii. We measured transepithelial electrical resistance (TEER) value (as an index of barrier function) and ovalbumin (OVA) permeation (as an index of permeability) to observe the changes of intestinal barrier function. The treatment of F. Arctii increased TEER value and decreased OVA influx on Caco-2 cell monolayers. Furthermore, we found that arctigenin as an active component of F. Arctii increased TEER value and reduced permeability of OVA from apical to the basolateral side but not arctiin. In the present study, we revealed that F. Arctii could enhance intestinal barrier function, and its active component was an arctigenin on the functionality. We expect that the arctigenin from F. Arctii could contribute to prevention of inflammatory, allergic, and infectious diseases by reinforcing intestinal barrier function. PMID:26550018

Advanced glycation endproducts form during ovalbumin digestion in the presence of fructose: Inhibition by chlorogenic acid.

Science.gov (United States)

Bains, Yasmin; Gugliucci, Alejandro; Caccavello, Russell

2017-07-01

One mechanism by which fructose could exert deleterious effects is through intestinal formation and absorption of pro-inflammatory advanced glycation endproducts via the Maillard reaction. We employed simulated stomach and duodenum digestion of ovalbumin (OVA) to test the hypothesis that advanced glycation endproducts (AGEs) are formed by fructose during simulated digestion of a ubiquitous food protein under model physiological conditions. OVA was subjected to simulated gastric and intestinal digestion using standard models, in presence of fructose or glucose (0-100mM). Peptide fractions were analyzed by fluorescence spectroscopy and intensity at Excitation: λ370nm, Emission: λ 440nm. AGE adducts formed between fructose and OVA, evidenced by the peptide fractions (fructose-AGE formation on a ubiquitous dietary protein under model physiological conditions. Our study also suggests ways to decrease the damage: enteral fructose-AGE formation may be partially inhibited by co-intake of beverages, fruits and vegetables with concentrations of phenolics high enough to serve as anti-glycation agents. Copyright © 2017 Elsevier B.V. All rights reserved.

Secretoglobin Superfamily Protein SCGB3A2 Deficiency Potentiates Ovalbumin-Induced Allergic Pulmonary Inflammation

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Taketomo Kido

2014-01-01

Full Text Available Secretoglobin (SCGB 3A2, a cytokine-like secretory protein of small molecular weight, which may play a role in lung inflammation, is predominantly expressed in airway epithelial cells. In order to understand the physiological role of SCGB3A2, Scgb3a2−/− mice were generated and characterized. Scgb3a2−/− mice did not exhibit any overt phenotypes. In ovalbumin- (OVA- induced airway allergy inflammation model, Scgb3a2−/− mice in mixed background showed a decreased OVA-induced airway inflammation, while six times C57BL/6NCr backcrossed congenic Scgb3a2−/− mice showed a slight exacerbation of OVA-induced airway inflammation as compared to wild-type littermates. These results indicate that the loss of SCGB3A2 function was influenced by a modifier gene(s in mixed genetic background and suggest that SCGB3A2 has anti-inflammatory property. The results further suggest the possible use of recombinant human SCGB3A2 as an anti-inflammatory agent.

No adjuvant effect of Bacillus thuringiensis-maize on allergic responses in mice.

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Daniela Reiner

Full Text Available Genetically modified (GM foods are evaluated carefully for their ability to induce allergic disease. However, few studies have tested the capacity of a GM food to act as an adjuvant, i.e. influencing allergic responses to other unrelated allergens at acute onset and in individuals with pre-existing allergy. We sought to evaluate the effect of short-term feeding of GM Bacillus thuringiensis (Bt-maize (MON810 on the initiation and relapse of allergic asthma in mice. BALB/c mice were provided a diet containing 33% GM or non-GM maize for up to 34 days either before ovalbumin (OVA-induced experimental allergic asthma or disease relapse in mice with pre-existing allergy. We observed that GM-maize feeding did not affect OVA-induced eosinophilic airway and lung inflammation, mucus hypersecretion or OVA-specific antibody production at initiation or relapse of allergic asthma. There was no adjuvant effect upon GM-maize consumption on the onset or severity of allergic responses in a mouse model of allergic asthma.

Arctigenin from Fructus Arctii (Seed of Burdock Reinforces Intestinal Barrier Function in Caco-2 Cell Monolayers

Directory of Open Access Journals (Sweden)

Hee Soon Shin

2015-01-01

Full Text Available Fructus Arctii is used as a traditional herbal medicine to treat inflammatory diseases in oriental countries. This study aimed to investigate effect of F. Arctii extract on intestinal barrier function in human intestinal epithelial Caco-2 cells and to reveal the active component of F. Arctii. We measured transepithelial electrical resistance (TEER value (as an index of barrier function and ovalbumin (OVA permeation (as an index of permeability to observe the changes of intestinal barrier function. The treatment of F. Arctii increased TEER value and decreased OVA influx on Caco-2 cell monolayers. Furthermore, we found that arctigenin as an active component of F. Arctii increased TEER value and reduced permeability of OVA from apical to the basolateral side but not arctiin. In the present study, we revealed that F. Arctii could enhance intestinal barrier function, and its active component was an arctigenin on the functionality. We expect that the arctigenin from F. Arctii could contribute to prevention of inflammatory, allergic, and infectious diseases by reinforcing intestinal barrier function.

The effect of vaccinating S. mansoni–infected BALB/c mice either ...

African Journals Online (AJOL)

kemrilib

Schistosoma mansoni eggs were obtained from faecal material of .... placed schistosome egg were measured using the ocular micrometer [12]. ..... The drop at week. 4 post-challenge could be attributed to lower antigen load as a result of few challenge parasites, compounded by death of challenge parasites as a result of ...

ORIGINAL ARTICLE 79

African Journals Online (AJOL)

User

1991: Human IgE, IgG4 and resistance to reinfection with Schistosoma mansoni. Nature,. 349; 243-245. 23. Andrews, P., (1986): Prazequantel: mechanisms of anti-schistosomal activity. Phamacology Theory, 29,129-156. 24. Gazzinelli G. Katz, N., Nocha, R.S., et al. 1985 Immune responses during human schistosomiasis ...

Effect of IL-1b and IL-1RN polymorphisms in carcinogenesis of the ...

African Journals Online (AJOL)

2016-06-22

Jun 22, 2016 ... Wroblewski LE, Peek RMJ, Wilson KT. Helicobacter pylori and gastric cancer: factors that modulate disease risk. Clin Micro- biol Rev. 2010; 23: 713Б39. 2. IARC Monographs on the Carcinogenic Risks to Humans. Schistosomes, Liver Flukes and Helicobacter Pylori, IARC. Monograph Vol. 61. Lyon, France: ...

Women with polycystic ovary syndrome demonstrate worsening markers of cardiovascular risk over the short-term despite declining hyperandrogenaemia: Results of a longitudinal study with community controls.

Science.gov (United States)

Huddleston, Heather G; Quinn, Molly M; Kao, Chia-Ning; Lenhart, Nikolaus; Rosen, Mitchell P; Cedars, Marcelle I

2017-12-01

To compare age-associated changes in cardiovascular risk markers in lean and obese reproductive-aged women with polycystic ovary syndrome (PCOS) with community controls. Longitudinal study at an academic medical centre PATIENTS: Patients diagnosed with PCOS by 2004 Rotterdam criteria in a multidisciplinary clinic were systematically enrolled from 2006-2014 in a PCOS cohort study and subsequently agreed to participate in a longitudinal study. The comparison controls were from the prospective, longitudinal Ovarian Aging (OVA) study, which consists of healthy women with regular menstrual cycles recruited from 2006 to 2011. Cardiovascular risk markers and hormone parameters at baseline and follow-up. Obese and lean PCOS (n = 38) and control women (n = 296) completed two study visits. The follow-up time (3.5 ± 1.5 vs 4.0 ± 0.8 years, P = .06) and magnitude of BMI gain (+0.1 kg/m 2 /y [-0.11, 0.36] vs +0.26 [-0.18, 0.87] P = .19) did not differ between obese and lean PCOS and controls. In PCOS subjects, total testosterone decreased in both obese and lean, but the decrease was greater in obese subjects (-0.09 nmol/L per year; 95% CI: -0.16, -0.02 vs -0.04 nmol/L per year; 95%CI: -0.11, 0.03). Compared to their respective controls, obese and lean PCOS saw worsening triglyceride (TG) levels (P women with PCOS demonstrated declines in biochemical hyperandrogenaemia over time. Despite this, PCOS subjects experienced steeper increases in cardiovascular risk factors associated with insulin resistance, including triglycerides and HOMA-IR. © 2017 John Wiley & Sons Ltd.

Berberine Attenuates Inflammation Associated with Delayed-Type Hypersensitivity via Suppressing Th1 Response and Inhibiting Apoptosis.

Science.gov (United States)

Wang, Zhigang; Chen, Zhe; Chen, Tao; Yi, Tao; Zheng, Zhou; Fan, Hong; Chen, Zebin

2017-02-01

Berberine, one of the active alkaloids from Rhizoma Coptidis, has been indicated to have anti-inflammatory and immunosuppressive properties. The aim of this study was to determine the role of berberine on ovalbumin (OVA)-induced delayed-type hypersensitivity (DTH) and its potential mechanisms. Berberine treatment significantly reduced footpad swelling, inflammatory cells infiltration, anti-OVA IgG levels, IgE concentration in serum, and the tetramer + CD8 + cells. In homogenized footpad tissue, the production of Th1-mediated cytokines including IFN-γ, TNF-α, and IL-2 were suppressed following the administration of berberine. Detailed studies revealed that berberine prevented differentiation into Th1 cells in the OVA-primed lymphocytes, resulting from suppressing the expression of T-bet and secretion of IFN-γ but not IL-4. Concanavalin A stimulation assay and MTT assay also indicated inhibiting effect of berberine treatment on IFN-γ production and decreased cytotoxicity in lymphocytes proliferation, respectively. Additionally, berberine obviously decreased the cell apoptosis and enzymatic activity of caspase-3, which was further confirmed by the facts that berberine clearly lowered Bax/Bcl-2 ratio and expression of cleaved caspase-3 protein. On correlation analysis, the percentage of apoptotic cells showed a significant positive relationship with IFN-γ/IL-4 ratio of supernatant from footpad tissue in berberine-treated DTH mice. These results demonstrated that berberine attenuated Th1-mediated inflammation in OVA-induced DTH by curbing Th1 response and inhibiting cell apoptosis, suggesting a therapeutic potential for berberine for the treatment of type IV hypersensitivity.

Exposure to Particulate Hexavalent Chromium Exacerbates Allergic Asthma Pathology

Science.gov (United States)

Schneider, Brent C.; Constant, Stephanie L.; Patierno, Steven R.; Jurjus, Rosalyn A.; Ceryak, Susan M.

2011-01-01

Airborne hexavalent chromate, Cr(VI), has been identified by the Environmental Protection Agency as a possible health threat in urban areas, due to the carcinogenic potential of some of its forms. Particulate chromates are produced in many different industrial settings, with high levels of aerosolized forms historically documented. Along with an increased risk of lung cancer, a high incidence of allergic asthma has been reported in workers exposed to certain inhaled particulate Cr(VI) compounds. However, a direct causal association between Cr(VI) and allergic asthma has not been established. We recently showed that inhaled particulate Cr(VI) induces an innate neutrophilic inflammatory response in BALB/c mice. In the current studies we investigated how the inflammation induced by inhaled particulate Cr(VI) might alter the pathology of an allergic asthmatic response. We used a well-established mouse model of allergic asthma. Groups of ovalbumin protein (OVA)-primed mice were challenged either with OVA alone, or with a combination of OVA and particulate zinc chromate, and various parameters associated with asthmatic responses were measured. Co-exposure to particulate Cr(VI) and OVA mediated a mixed form of asthma in which both eosinophils and neutrophils are present in airways, tissue pathology is markedly exacerbated, and airway hyperresponsiveness is significantly increased. Taken together these findings suggest that inhalation of particulate forms of Cr(VI) may augment the severity of ongoing allergic asthma, as well as alter its phenotype. Such findings may have implications for asthmatics in settings in which airborne particulate Cr(VI) compounds are present at high levels. PMID:22178736

Repurposing drugs for the treatment and control of helminth infections

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Gordana Panic

2014-12-01

Full Text Available Helminth infections are responsible for a considerable public health burden, yet the current drug armamentarium is small. Given the high cost of drug discovery and development, the high failure rates and the long duration to develop novel treatments, drug repurposing circumvents these obstacles by finding new uses for compounds other than those they were initially intended to treat. In the present review, we summarize in vivo and clinical trial findings testing clinical candidates and marketed drugs against schistosomes, food-borne trematodes, soil-transmitted helminths, Strongyloides stercoralis, the major human filariases lymphatic filariasis and onchocerciasis, taeniasis, neurocysticercosis and echinococcosis. While expanding the applications of broad-spectrum or veterinary anthelmintics continues to fuel alternative treatment options, antimalarials, antibiotics, antiprotozoals and anticancer agents appear to be producing fruitful results as well. The trematodes and nematodes continue to be most investigated, while cestodal drug discovery will need to be accelerated. The most clinically advanced drug candidates include the artemisinins and mefloquine against schistosomiasis, tribendimidine against liver flukes, oxantel pamoate against trichuriasis, and doxycycline against filariasis. Preclinical studies indicate a handful of promising future candidates, and are beginning to elucidate the broad-spectrum activity of some currently used anthelmintics. Challenges and opportunities are further discussed.

Characterization of the cGMP-dependent protein kinase SmcGK1 of Schistosoma mansoni

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Silke Leutner

2011-06-01

Full Text Available Schistosomes are trematode parasites and of worldwide medical importance for humans and animals. Growth and development of these parasites require a specific host environment, but also permanent communication processes between the two genders. Accumulating molecular evidence indicates that the responsible interactions are mediated by signal transduction processes. Conserved signaling molecules were identified, and first approaches made for their characterization. However, no representative of the conserved family of cGMP-dependent protein kinases (cGKs has been described in this parasite yet. Within the Schistosoma mansoni genome data-set we identified cGK homologs, of which one was investigated in more detail in this study. We present the cloning of SmcGK1, whose sequence shows homology to cGKs of higher eukaryotes. SmcGK1 was found to be gender-independently transcribed in adult schistosomes. The occurrence of SmcGK1 sense and antisense transcripts suggests that the expression of this gene is controlled at the post-transcriptional level. In situ hybridization experiments demonstrated a gonad-preferential expression profile in both genders indicating a role of SmcGK1, at least during sexual development of schistosomes. Using a cGK-specific inhibitor to treat adult schistosomes in vitro finally resulted in a multifaceted phenotype including slow motion, oocyte congestion, and reduced egg production.Esquistossomos são parasitas trematodos de importância médica em todo o mundo para o homem e os animais. O crescimento e o desenvolvimento destes parasitas requerem um ambiente específico do hospedeiro, mas também um processo de comunicação permanente entre parasitas dos dois sexos. Evidência molecular tem se acumulado e indica que as interações são mediadas por processos de transdução de sinal. Moléculas sinalizadoras conservadas foram identificadas, e as primeiras abordagens têm sido feitas para sua caracterização. Contudo, não foi

A “ray of hope” for European stem cell patents or “out of the smog into the fog”?

DEFF Research Database (Denmark)

Nordberg, Ana; Minssen, Timo

2016-01-01

In Case C-364/13 International Stem Cell Corporation (ISCC) v. Comptroller General of Patents (December 18th, 2014), the Court of Justice of the European Union (CJEU) distinguished its’ earlier ruling in Brüstle v. Greenpeace (Brüstle) with regard to non-fertilized human ova stimulated by parthen......In Case C-364/13 International Stem Cell Corporation (ISCC) v. Comptroller General of Patents (December 18th, 2014), the Court of Justice of the European Union (CJEU) distinguished its’ earlier ruling in Brüstle v. Greenpeace (Brüstle) with regard to non-fertilized human ova stimulated...

Differences in allergic inflammatory responses between urban PM2.5 and fine particle derived from desert-dust in murine lungs

Energy Technology Data Exchange (ETDEWEB)

He, Miao, E-mail: hemiao@mail.cmu.edu.cn [Environment and Non-communicable Disease Research Center, School of Public Health, China Medical University, Shenyang 110122 (China); Department of Health Sciences, Oita University of Nursing and Health Sciences, Oita 870-1201 (Japan); Ichinose, Takamichi, E-mail: ichinose@oita-nhs.ac.jp [Department of Health Sciences, Oita University of Nursing and Health Sciences, Oita 870-1201 (Japan); Kobayashi, Makoto [Department of Respiratory Medicine, Kanazawa Medical University, Ishikawa 920-0293 (Japan); Arashidani, Keiichi [Department of Immunology and Parasitology, School of Medicine, University of Occupational and Environmental Health, Fukuoka 807-8555 (Japan); Yoshida, Seiichi [Department of Health Sciences, Oita University of Nursing and Health Sciences, Oita 870-1201 (Japan); Nishikawa, Masataka [Environmental Chemistry Division, National Institute for Environmental Studies, Ibaraki 305-8506 (Japan); Takano, Hirohisa [Environmental Health Division, Department of Environmental Engineering, Graduate School of Engineering, Kyoto University, Kyoto 615-8530 (Japan); Sun, Guifan [Environment and Non-communicable Disease Research Center, School of Public Health, China Medical University, Shenyang 110122 (China); Shibamoto, Takayuki [Department of Environmental Toxicology, University of California, Davis, CA 95616 (United States)

2016-04-15

The biological and chemical natures of materials adsorbed onto fine particulate matter (PM2.5) vary by origin and passage routes. The exacerbating effects of the two samples—urban PM2.5 (U-PM2.5) collected during the hazy weather in a Chinese city and fine particles (ASD-PM2.5) collected during Asian sand dust (ASD) storm event days in Japan—on murine lung eosinophilia were compared to clarify the role of toxic materials in PM2.5. The amounts of β-glucan and mineral components were higher in ASD-PM2.5 than in U-PM2.5. On the other hand, organic chemicals, including polycyclic aromatic hydrocarbons (PAHs), were higher in U-PM2.5 than in ASD-PM2.5. When BALB/c mice were intratracheally instilled with U-PM2.5 and ASD-PM2.5 (total 0.4 mg/mouse) with or without ovalbumin (OVA), various biological effects were observed, including enhancement of eosinophil recruitment induced by OVA in the submucosa of the airway, goblet cell proliferation in the bronchial epithelium, synergic increase of OVA-induced eosinophil-relevant cytokines and a chemokine in bronchoalveolar lavage fluid, and increase of serum OVA-specific IgG1 and IgE. Data demonstrate that U-PM2.5 and ASD-PM2.5 induced allergic inflammatory changes and caused lung pathology. U-PM2.5 and ASD-PM2.5 increased F4/80{sup +} CD11b{sup +} cells, indicating that an influx of inflammatory and exudative macrophages in lung tissue had occurred. The ratio of CD206 positive F4/80{sup +} CD11b{sup +} cells (M2 macrophages) in lung tissue was higher in the OVA + ASD-PM2.5 treated mice than in the OVA + U-PM2.5 treated mice. These results suggest that the lung eosinophilia exacerbated by both PM2.5 is due to activation of a Th2-associated immune response along with induced M2 macrophages and the exacerbating effect is greater in microbial element (β-glucan)-rich ASD-PM2.5 than in organic chemical-rich U-PM2.5. - Highlights: • The aggravating effects of urban-PM2.5 and desert-PM2.5 on lung eosinophilia were compared. �

Differences in allergic inflammatory responses between urban PM2.5 and fine particle derived from desert-dust in murine lungs

International Nuclear Information System (INIS)

He, Miao; Ichinose, Takamichi; Kobayashi, Makoto; Arashidani, Keiichi; Yoshida, Seiichi; Nishikawa, Masataka; Takano, Hirohisa; Sun, Guifan; Shibamoto, Takayuki

2016-01-01

The biological and chemical natures of materials adsorbed onto fine particulate matter (PM2.5) vary by origin and passage routes. The exacerbating effects of the two samples—urban PM2.5 (U-PM2.5) collected during the hazy weather in a Chinese city and fine particles (ASD-PM2.5) collected during Asian sand dust (ASD) storm event days in Japan—on murine lung eosinophilia were compared to clarify the role of toxic materials in PM2.5. The amounts of β-glucan and mineral components were higher in ASD-PM2.5 than in U-PM2.5. On the other hand, organic chemicals, including polycyclic aromatic hydrocarbons (PAHs), were higher in U-PM2.5 than in ASD-PM2.5. When BALB/c mice were intratracheally instilled with U-PM2.5 and ASD-PM2.5 (total 0.4 mg/mouse) with or without ovalbumin (OVA), various biological effects were observed, including enhancement of eosinophil recruitment induced by OVA in the submucosa of the airway, goblet cell proliferation in the bronchial epithelium, synergic increase of OVA-induced eosinophil-relevant cytokines and a chemokine in bronchoalveolar lavage fluid, and increase of serum OVA-specific IgG1 and IgE. Data demonstrate that U-PM2.5 and ASD-PM2.5 induced allergic inflammatory changes and caused lung pathology. U-PM2.5 and ASD-PM2.5 increased F4/80 + CD11b + cells, indicating that an influx of inflammatory and exudative macrophages in lung tissue had occurred. The ratio of CD206 positive F4/80 + CD11b + cells (M2 macrophages) in lung tissue was higher in the OVA + ASD-PM2.5 treated mice than in the OVA + U-PM2.5 treated mice. These results suggest that the lung eosinophilia exacerbated by both PM2.5 is due to activation of a Th2-associated immune response along with induced M2 macrophages and the exacerbating effect is greater in microbial element (β-glucan)-rich ASD-PM2.5 than in organic chemical-rich U-PM2.5. - Highlights: • The aggravating effects of urban-PM2.5 and desert-PM2.5 on lung eosinophilia were compared. • Both PM2.5 enhanced

[Strategy of comprehensive control for schistosomiasis and its effect in key areas of Jiangsu Province].

Science.gov (United States)

Sun, Le-Ping; Tian, Zeng-Xi; Yang, Kun; Hong, Qing-Biao; Gao, Yang; Gao, Yuan; Zhang, Lian-Heng; Yang, Guo-Jing; Min, Jie; Ge, Jun; Wu, Hong-Hui; Huang, Yi-Xin; Liang, You-Sheng

2011-12-01

implementation of comprehensive control, the settings with infected snails, infected snail areas, infection rates of snails reduced from 75, 802.73 hm2 and 0.10% before the comprehensive control in 2007 to all 0 in 2010, with reduction rates of all 100%. The infection rates of schistosome in both humans and domestic animals appeared declining trends in 12 counties (districts) from 2005 to 2010, and the human infection rates were 0.16%, 0.04%, 0.02%, 0.02%, 0.01% and 0.01%, respectively, while being 0.11%, 0.05%, 0, 0, 0 and 0, respectively in domestic animals. During the period of comprehensive control, totally 45 transmission-controlled townships and 183 villages were newly added. In 2010, all of the 12 counties (districts) reached the criteria of schistosomiasis transmission control. The comprehensive control with emphasis on the key areas where infected snails are found, is an effective measure to further facilitate schistosomiasis control and rapidly control the transmission of schistosomiasis.

Upregulation of B7 molecules (CD80 and CD86) and exacerbated eosinophilic pulmonary inflammatory response in mice lacking the IFN-beta gene

DEFF Research Database (Denmark)

Matheu, Victor; Treschow, Alexandra; Navikas, Vaidrius

2003-01-01

. OBJECTIVE: We sought to define the differential role of endogenous IFN-beta in controlling the development of allergic inflammation. METHODS: We assessed whether deletion of the gene encoding IFN-beta (IFNB) with knockout mice participated in the development of allergic response in ovalbumin (OVA......BACKGROUND: IFN-beta has been shown to be effective as therapy for multiple sclerosis. Some reports attributed its beneficial effects to the capacity to induce a T(H)2 response. However, other studies have suggested that endogenous type I IFN might downregulate the allergic response in mice...

Cathepsin-D And Tnf-α in Bladder Cancer

Directory of Open Access Journals (Sweden)

T. Salman

1996-01-01

Full Text Available In a study of 34 normal healthy controls, 35 patients with urinary tract bilharziasis and 93 bladder cancer patients (62 of them are operable cases and 31 are non-operable ones, serum tumor necrosis factor alpha (TNF-α and cytosolic Cathepsin-D were estimated. Though both potential markers were elevated in bladder cancer patients, neither Cathepsin-D nor TNF-α showed associations of prognostic value since there were no positive correlations with tumor stages, grades or association of tumors with bilharzia ova or lymph node involvement.

Multiple helminth infection of the skin causes lymphocyte hypo-responsiveness mediated by Th2 conditioning of dermal myeloid cells.

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Peter C Cook

2011-03-01

Full Text Available Infection of the mammalian host by schistosome larvae occurs via the skin, although nothing is known about the development of immune responses to multiple exposures of schistosome larvae, and/or their excretory/secretory (E/S products. Here, we show that multiple (4x exposures, prior to the onset of egg laying by adult worms, modulate the skin immune response and induce CD4(+ cell hypo-responsiveness in the draining lymph node, and even modulate the formation of hepatic egg-induced granulomas. Compared to mice exposed to a single infection (1x, dermal cells from multiply infected mice (4x, were less able to support lymph node cell proliferation. Analysis of dermal cells showed that the most abundant in 4x mice were eosinophils (F4/80(+MHC-II(-, but they did not impact the ability of antigen presenting cells (APC to support lymphocyte proliferation to parasite antigen in vitro. However, two other cell populations from the dermal site of infection appear to have a critical role. The first comprises arginase-1(+, Ym-1(+ alternatively activated macrophage-like cells, and the second are functionally compromised MHC-II(hi cells. Through the administration of exogenous IL-12 to multiply infected mice, we show that these suppressive myeloid cell phenotypes form as a consequence of events in the skin, most notably an enrichment of IL-4 and IL-13, likely resulting from an influx of RELMα-expressing eosinophils. We further illustrate that the development of these suppressive dermal cells is dependent upon IL-4Rα signalling. The development of immune hypo-responsiveness to schistosome larvae and their effect on the subsequent response to the immunopathogenic egg is important in appreciating how immune responses to helminth infections are modulated by repeated exposure to the infective early stages of development.

Down regulation of the TCR complex CD3 ζ-chain on CD3+ T cells: a potential mechanism for helminth mediated immune modulation

Directory of Open Access Journals (Sweden)

Laura Jane Appleby

2015-02-01

Full Text Available The CD3ζ forms part of the T cell receptor (TCR where it plays an important role in coupling antigen recognition to several intracellular signal-transduction pathways leading to T cell effector functions. Down regulation of CD3ζ leads to impairment of immune responses including reduced cell proliferation and cytokine production. In experimental models helminth parasites have been shown to modulate immune responses directed against them and unrelated antigens, so called bystander antigens, but there is a lack of studies validating these observations in humans. This study focused on investigated the relationship between expression levels of the TCR CD3ζ chain with lymphocyte cell proliferation during human infection with the helminth parasite, Schistosoma haematobium which causes uro-genital schistosomiasis. Using flow cytometry, peripheral blood mononuclear cells (PBMCs from individuals naturally exposed to S. haematobium in rural Zimbabwe were phenotyped, and expression levels of CD3ζ on T cells were related to intensity of infection. In this population, parasite infection intensity was inversely related to CD3ζ expression levels (p<0.05, consistent with down-regulation of CD3ζ expression during helminth infection. Furthermore, PBMC proliferation was positively related to expression levels of CD3ζ (p<0.05 after allowing for confounding variables (host age, sex, infection level. CD3ζ expression levels had a differing relationship between immune correlates of susceptibility and immunity, measured by antibody responses, indicating a complex relationship between immune activation status and immunity. The relationships between the CD3ζ chain of the TCR and schistosome infection, PBMC proliferation and schistosome-specific antibody responses have not previously been reported, and these results may indicate a mechanism for the impaired T cell proliferative responses observed during human schistosome infection.

Helminth Infection and Commensal Microbiota Drive Early IL-10 Production in the Skin by CD4+ T Cells That Are Functionally Suppressive.

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David E Sanin

2015-05-01

Full Text Available The skin provides an important first line of defence and immunological barrier to invasive pathogens, but immune responses must also be regulated to maintain barrier function and ensure tolerance of skin surface commensal organisms. In schistosomiasis-endemic regions, populations can experience repeated percutaneous exposure to schistosome larvae, however little is known about how repeated exposure to pathogens affects immune regulation in the skin. Here, using a murine model of repeated infection with Schistosoma mansoni larvae, we show that the skin infection site becomes rich in regulatory IL-10, whilst in its absence, inflammation, neutrophil recruitment, and local lymphocyte proliferation is increased. Whilst CD4+ T cells are the primary cellular source of regulatory IL-10, they expressed none of the markers conventionally associated with T regulatory (Treg cells (i.e. FoxP3, Helios, Nrp1, CD223, or CD49b. Nevertheless, these IL-10+ CD4+ T cells in the skin from repeatedly infected mice are functionally suppressive as they reduced proliferation of responsive CD4+ T cells from the skin draining lymph node. Moreover, the skin of infected Rag-/- mice had impaired IL-10 production and increased neutrophil recruitment. Finally, we show that the mechanism behind IL-10 production by CD4+ T cells in the skin is due to a combination of an initial (day 1 response specific to skin commensal bacteria, and then over the following days schistosome-specific CD4+ T cell responses, which together contribute towards limiting inflammation and tissue damage following schistosome infection. We propose CD4+ T cells in the skin that do not express markers of conventional T regulatory cell populations have a significant role in immune regulation after repeated pathogen exposure and speculate that these cells may also help to maintain skin barrier function in the context of repeated percutaneous insult by other skin pathogens.

in human Africa South The importance of animals schistosomiasis in

African Journals Online (AJOL)

Africa. South. The importance of animals schistosomiasis in. J. A. VAN WYK. Suinmary. The importance of animals in human schistosomia- sis in South Africa is reviewed. The prevalence of animal schistosome species in humans, the role of animals as reservoir hosts of .... that it is not of pure origin? More work is necessary, ...

Evidence against the existence of specific Schistosoma mansoni subpopulations which are resistant to irradiated vaccine-induced immunity

International Nuclear Information System (INIS)

Lewis, F.A.; Hieny, S.; Sher, A.

1985-01-01

When mice are immunized with irradiated Schistosoma mansoni cercariae a proportion of the subsequent cercarial challenge always escapes killing and matures to egg-laying adults. This report investigates the possibility that incomplete immunity in this system is governed by a genetically-determined insusceptibility of a particular schistosome subpopulation. To do this the authors tested whether more immunoresistant schistosomes would develop following successive passages of progeny of the resistant worms through immunized mice. Mice were immunized with 500 50 Krad-irradiated cercariae, and challenged with normal cercariae when immunity was at its peak. After five successive passages through snails and immune mice, progeny of those parasites which escaped immune killing were no more refractory to vaccine-induced resistance than the original stock maintained in nonimmune mice. Additionally, the passaged isolates did not differ from the original stock in their ability to induce protection following irradiation. The results indicate that with this model of acquired resistance incomplete immunity is unlikely to be due to a subpopulation of the parasites possessing a genetically-determined insusceptibility to killing

Schistosoma mansoni: parasitology and immunology of baboons vaccinated with irradiated cryopreserved schistosomula

Energy Technology Data Exchange (ETDEWEB)

Damian, R.T.; Powell, M.R.; Roberts, M.L. (Georgia Univ., Athens (USA). Dept. of Zoology); Clark, J.D. (Georgia Univ., Athens (USA). Lab. Animal Medicine); Stirewalt, M.A.; Lewis, F.A. (Biomedical Research Inst., Rockville, MD (USA))

1985-06-01

Young baboons (Papio cynocephalus) were vaccinated with ..gamma..-irradiated (500 Gy) cryopreserved Puerto Rican strain schistosomula of S. mansoni. Protection against heterologous, normal Kenyan Strain S. mansoni challenge infection was erratic and partial; and two putative correlates of immunity, reduced worm fecundity and change in worm location (anterior shift) were not observed. However, immunization of baboons with this vaccine resulted in a stimulated immune system. Both cellular and humoral anamnesis were demonstrable in vaccinated-challenged baboons. Schistosome infection-associated IgM hypergammaglobulinemia was also greatly reduced in vaccinated-challenged baboons. However IgG antibodies to adult, egg, and cercarial antigens were increased after challenge infection in preimmunized baboons. Vaccination appears to have resulted in a redirection of the immune system into anti-parasite channels, but this more specific immune response was insufficient to confer good protection against challenge infection in this experiment. The dampening effect of the vaccine on the hypergammaglobulinemia of schistosomiasis is another candidate for a possible ''anti-pathogenesis'' effect of irradiated schistosome larval vaccines.

Schistosoma mansoni: parasitology and immunology of baboons vaccinated with irradiated cryopreserved schistosomula

International Nuclear Information System (INIS)

Damian, R.T.; Powell, M.R.; Roberts, M.L.

1985-01-01

Young baboons (Papio cynocephalus) were vaccinated with γ-irradiated (500 Gy) cryopreserved Puerto Rican strain schistosomula of S. mansoni. Protection against heterologous, normal Kenyan Strain S. mansoni challenge infection was erratic and partial; and two putative correlates of immunity, reduced worm fecundity and change in worm location (anterior shift) were not observed. However, immunization of baboons with this vaccine resulted in a stimulated immune system. Both cellular and humoral anamnesis were demonstrable in vaccinated-challenged baboons. Schistosome infection-associated IgM hypergammaglobulinemia was also greatly reduced in vaccinated-challenged baboons. However IgG antibodies to adult, egg, and cercarial antigens were increased after challenge infection in preimmunized baboons. Vaccination appears to have resulted in a redirection of the immune system into anti-parasite channels, but this more specific immune response was insufficient to confer good protection against challenge infection in this experiment. The dampening effect of the vaccine on the hypergammaglobulinemia of schistosomiasis is another candidate for a possible ''anti-pathogenesis'' effect of irradiated schistosome larval vaccines. (author)

Functional genomic characterization of neoblast-like stem cells in larval Schistosoma mansoni

Science.gov (United States)

Wang, Bo; Collins, James J; Newmark, Phillip A

2013-01-01

Schistosomes infect hundreds of millions of people in the developing world. Transmission of these parasites relies on a stem cell-driven, clonal expansion of larvae inside a molluscan intermediate host. How this novel asexual reproductive strategy relates to current models of stem cell maintenance and germline specification is unclear. Here, we demonstrate that this proliferative larval cell population (germinal cells) shares some molecular signatures with stem cells from diverse organisms, in particular neoblasts of planarians (free-living relatives of schistosomes). We identify two distinct germinal cell lineages that differ in their proliferation kinetics and expression of a nanos ortholog. We show that a vasa/PL10 homolog is required for proliferation and maintenance of both populations, whereas argonaute2 and a fibroblast growth factor receptor-encoding gene are required only for nanos-negative cells. Our results suggest that an ancient stem cell-based developmental program may have enabled the evolution of the complex life cycle of parasitic flatworms. DOI: http://dx.doi.org/10.7554/eLife.00768.001 PMID:23908765

Schistosoma mansoni infection in a fishermen community, the Lake Manzala region-Egypt

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Amira Taman

2014-12-01

Full Text Available Objective: To determine the prevalence of schistosomiasis in the fishermen community in Egypt. Methods: A cross-sectional survey for schistosomiasis mansoni was conducted among 150 fishermen and their families from January to November 2013. Faecal samples were examined by Kato Katz method and formalin-ether concentration technique. Malacological survey was conducted to identify infection of the snail intermediate host by larval stage of Schistosoma mansoni. Snails were collected and checked for shedding of cercariae after light exposure. Results: Overall prevalence of infection was 26.6% with an intensity of (42.7依7.2 ova/g of stool. Infection was common in male and significantly increased in the age of 20-40 years. Praziquanteltreated individuals had a high significant decrease in intensity (27.2依2.4 ova/g of stool than those with no treatment history. Biomphalaria alexandrina snail was infected with Schistosoma mansoni particularly in warm seasons and mice infection was established successfully from the shed cercariae, moreover adult worms were obtained via portal perfusion of the infected mice. Conclusions: Findings indicated the endemicity of schistosomiasis mansoni in Lake Manzala region, therefore, appropriate integrated control measures are needed among fishermen including health education, environmental sanitation, periodic screening and mass treatment with praziquantel.

Development of a Loop Mediated Isothermal Amplification for Diagnosis of Ascaris lumbricoides in Fecal Samples

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Esther A. Shiraho

2016-01-01

Full Text Available Ascaris lumbricoides is a nematode parasite that causes the common tropical infection ascariasis in humans. It is also considered among the neglected tropical diseases. Diagnosis relies mainly on microscopy-based methods which are laborious, are limited by low sensitivity, and require high expertise. We have developed a loop mediated isothermal amplification (LAMP for diagnosis of ascariasis in fecal samples, based on the first internal transcribed (ITS-1 spacer region of the ribosomal DNA. We used Primer Explorer V4 software to design primers. Ascaris adult and ova were obtained from naturally infected school children, whose parents/guardians gave consent for their participation in the study. Genomic DNA was extracted using alkaline lysis method and amplified by LAMP at 63°C for 45 minutes. LAMP products were visualized by naked eyes after adding SYBR Green dye and also on agarose gel. LAMP successfully and reliably detected Ascaris DNA from a single egg and in fecal samples. The assay specifically detected Ascaris DNA without amplifying DNA from ova of other parasites which commonly coexist with A. lumbricoides in feces. The developed LAMP assay has great potential for use in ascariasis diagnosis at the point of care and in low infection intensity situation that characterize control and elimination campaigns.

Trefoil factor-2 reverses airway remodeling changes in allergic airways disease.

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Royce, Simon G; Lim, Clarice; Muljadi, Ruth C; Samuel, Chrishan S; Ververis, Katherine; Karagiannis, Tom C; Giraud, Andrew S; Tang, Mimi L K

2013-01-01

Trefoil factor 2 (TFF2) is a small peptide with an important role in mucosal repair. TFF2 is up-regulated in asthma, suggesting a role in asthma pathogenesis. Given its known biological role in promoting epithelial repair, TFF2 might be expected to exert a protective function in limiting the progression of airway remodeling in asthma. The contribution of TFF2 to airway remodeling in asthma was investigated by examining the expression of TFF2 in the airway and lung, and evaluating the effects of recombinant TFF2 treatment on established airway remodeling in a murine model of chronic allergic airways disease (AAD). BALB/c mice were sensitized and challenged with ovalbumin (OVA) or saline for 9 weeks, whereas mice with established OVA-induced AAD were treated with TFF2 or vehicle control (intranasally for 14 d). Effects on airway remodeling, airway inflammation, and airway hyperresponsiveness were then assessed, whereas TFF2 expression was determined by immunohistochemistry. TFF2 expression was significantly increased in the airways of mice with AAD, compared with expression levels in control mice. TFF2 treatment resulted in reduced epithelial thickening, subepithelial collagen deposition, goblet-cell metaplasia, bronchial epithelium apoptosis, and airway hyperresponsiveness (all P < 0.05, versus vehicle control), but TFF2 treatment did not influence airway inflammation. The increased expression of endogenous TFF2 in response to chronic allergic inflammation is insufficient to prevent the progression of airway inflammation and remodeling in a murine model of chronic AAD. However, exogenous TFF2 treatment is effective in reversing aspects of established airway remodeling. TFF2 has potential as a novel treatment for airway remodeling in asthma.

Carrier protein influences immunodominance of a known epitope: implication in peptide vaccine design.

Science.gov (United States)

Ghosh, Moumita; Solanki, Ashish K; Roy, Koushik; Dhoke, Reema R; Ashish; Roy, Syamal

2013-09-23

We investigated how the processing of a given antigen by antigen presenting cells (APC) is dictated by the conformation of the antigen and how this governs the immunodominance hierarchy. To address the question, a known immunodominant sequence of bacteriophage lambda repressor N-terminal sequence 12-26 [λR(12-26)] was engineered at the N and C termini of a heterologous leishmanial protein, Kinetoplastid membrane protein-11 (KMP-11); the resulting proteins were defined as N-KMP-11 and C-KMP-11 respectively. The presence of λR(12-26) in N-KMP-11 and C-KMP-11 was established by western blot analysis with antibody to λR(12-26) peptide. N-KMP-11 but not C-KMP-11 could stimulate the anti λR(12-26) T-cell clonal population very efficiently in the presence of APCs. Priming of BALB/c mice with N-KMP-11 or C-KMP-11 generated similar levels of anti-KMP-11 IgG, but anti-λR(12-26) specific IgG was observed only upon priming with N-KMP-11. Interestingly, uptake of both N-KMP-11 and C-KMP-11 by APCs was similar but catabolism of N-KMP-11 but not C-KMP-11 was biphasic and fast at the initial time point. Kratky plots of small angle X-ray scattering showed that while N-KMP-11 adopts flexible Gaussian type of topology, C-KMP-11 prefers Globular nature. To show that KMP-11 is not unique as a carrier protein, an epitope (SPITBTNLBTMBK) of Plasmodium yoelii (PY) apical membrane protein 1[AMA-1 (136-148)], is placed at the C and N terminals of a dominant T-cell epitope of ovalbumin protein OVA(323-339) and the resulting peptides are defined as PY-OVA and OVA-PY respectively. Interestingly, only OVA-PY could stimulate anti-OVA T-cells and produce IgG response upon priming of BALB/c mice with it. Thus for rational design of peptide vaccine it is important to place the dominant epitope appropriately in the context of the carrier protein. Copyright © 2013 Elsevier Ltd. All rights reserved.

High Fat Diet Inhibits Dendritic Cell and T Cell Response to Allergens but Does Not Impair Inhalational Respiratory Tolerance.

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Angela Pizzolla

Full Text Available The incidence of obesity has risen to epidemic proportions in recent decades, most commonly attributed to an increasingly sedentary lifestyle, and a 'western' diet high in fat and low in fibre. Although non-allergic asthma is a well-established co-morbidity of obesity, the influence of obesity on allergic asthma is still under debate. Allergic asthma is thought to result from impaired tolerance to airborne antigens, so-called respiratory tolerance. We sought to investigate whether a diet high in fats affects the development of respiratory tolerance. Mice fed a high fat diet (HFD for 8 weeks showed weight gain, metabolic disease, and alteration in gut microbiota, metabolites and glucose metabolism compared to age-matched mice fed normal chow diet (ND. Respiratory tolerance was induced by repeated intranasal (i.n. administration of ovalbumin (OVA, prior to induction of allergic airway inflammation (AAI by sensitization with OVA in alum i.p. and subsequent i.n. OVA challenge. Surprisingly, respiratory tolerance was induced equally well in HFD and ND mice, as evidenced by decreased lung eosinophilia and serum OVA-specific IgE production. However, in a pilot study, HFD mice showed a tendency for impaired activation of airway dendritic cells and regulatory T cells compared with ND mice after induction of respiratory tolerance. Moreover, the capacity of lymph node cells to produce IL-5 and IL-13 after AAI was drastically diminished in HFD mice compared to ND mice. These results indicate that HFD does not affect the inflammatory or B cell response to an allergen, but inhibits priming of Th2 cells and possibly dendritic cell and regulatory T cell activation.

Erythrocyte Saturation with IgG Is Required for Inducing Antibody-Mediated Immune Suppression and Impacts Both Erythrocyte Clearance and Antigen-Modulation Mechanisms.

Science.gov (United States)

Cruz-Leal, Yoelys; Marjoram, Danielle; Lazarus, Alan H

2018-02-15

Anti-D prevents hemolytic disease of the fetus and newborn, and this mechanism has been referred to as Ab-mediated immune suppression (AMIS). Anti-D, as well as other polyclonal AMIS-inducing Abs, most often induce both epitope masking and erythrocyte clearance mechanisms. We have previously observed that some Abs that successfully induce AMIS effects could be split into those that mediate epitope masking versus those that induce erythrocyte clearance, allowing the ability to analyze these mechanisms separately. In addition, AMIS-inducing activity has recently been shown to induce Ag modulation (Ag loss from the erythrocyte surface). To assess these mechanisms, we immunized mice with transgenic murine RBCs expressing a single Ag protein comprising a recombinant Ag composed of hen egg lysozyme, OVA sequences comprising aa 251-349, and the human Duffy transmembrane protein (HOD-Ag) with serial doses of polyclonal anti-OVA IgG as the AMIS-inducing Ab. The anti-OVA Ab induced AMIS in the absence of apparent epitope masking. AMIS occurred only when the erythrocytes appeared saturated with IgG. This Ab was capable of inducing HOD-RBC clearance, as well as loss of the OVA epitope at doses of Ab that caused AMIS effects. HOD-RBCs also lost reactivity with Abs specific for the hen egg lysozyme and Duffy portions of the Ag consistent with the initiation of Ag modulation and/or trogocytosis mechanisms. These data support the concept that an AMIS-inducing Ab that does not cause epitope masking can induce AMIS effects in a manner consistent with RBC clearance and/or Ag modulation. Copyright © 2018 by The American Association of Immunologists, Inc.

An extract of the medicinal mushroom Agaricus blazei Murill can protect against allergy

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Hetland Geir

2009-05-01

Full Text Available Abstract Background Agaricus blazei Murill (AbM is an edible Brazilian mushroom that has been used in traditional medicine for a range of diseases. It has been shown to have anti-infection and anti-tumor properties in the mouse, which are due to induction of Th1 responses. On the other hand, IgE-mediated allergy is induced by a Th2 response. Objective Since according to the Th1/Th2 paradigm an increased Th1 response may promote a reduced Th2 response, the aim was to examine whether AbM had anti-allergy effects. Methods A mouse model for allergy was employed, in which the mice were immunized s.c. with the model allergen ovalbumin (OVA. Additionally, the animals were given a mushroom extract, AndoSan™, mainly (82% containing AbM, but also Hericium erinaceum (15% and Grifola frondosa (3%, or PBS p.o. either a day before or 19 days after the immunization. The mice were sacrificed on day 26, and anti-OVA IgE (Th2 response and IgG2a (Th1 response antibodies were examined in serum and Th1, Th2 and Treg cytokines in spleen cells cultures. Results It was found that the AndoSan™ extract both when given either before or after OVA immunization reduced the levels of anti-OVA IgE, but not IgG2a, in the mice. There was a tendency to reduced Th2 relative to Th1 cytokine levels in the AndoSan™ groups. Conclusion This particular AbM extract may both prevent allergy development and be used as a therapeutical substance against established allergy.

Effects of hybridization between nonnative Rainbow Trout and native Westslope Cutthroat Trout on fitness-related traits

Science.gov (United States)

Drinan, Daniel P.; Webb, Molly A. H.; Naish, Kerry A.; Kalinowski, Steven T.; Boyer, Matthew C.; Steed, Amber C.; Shepard, Bradley B.; Muhlfeld, Clint C.

2015-01-01

Hybridization between introduced and native fauna is a risk to native species and may threaten the long-term persistence of numerous taxa. Rainbow Trout Oncorhynchus mykiss has been one of the most widely introduced species around the globe and often hybridizes with native Cutthroat Trout O. clarkii in the Rocky Mountains. Previous work has shown that hybridization negatively affects reproductive success, but identification of the traits contributing to that reduction has been elusive. In this study, we used a combination of field and laboratory techniques to assess how hybridization with Rainbow Trout affects seven traits during several stages of Westslope Cutthroat Trout development: embryonic survival, ova size, ova energy concentration, sperm motility, juvenile weight, juvenile survival, and burst swimming endurance. Rainbow Trout admixture was correlated with an increase in embryonic survival and ova energy concentration but with a decrease in juvenile weight and burst swimming endurance. These correlations differed from previously observed patterns of reproductive success and likely do not explain the declines in reproductive success associated with admixture. Future investigation of additional, unstudied traits and the use of different environments may shed light on the traits responsible for reproductive success in admixed Cutthroat Trout.

Ghrelin Ameliorates Asthma by Inhibiting Endoplasmic Reticulum Stress.

Science.gov (United States)

Fu, Tian; Wang, Lei; Zeng, Qingdi; Zhang, Yan; Sheng, Baowei; Han, Liping

2017-12-01

This study aimed to confirm the ameliorative effect of ghrelin on asthma and investigate its mechanism. The murine model of asthma was induced by ovalbumin (OVA) treatment and assessed by histological pathology and airway responsiveness to methacholine. The total and differential leukocytes were counted. Tumor necrosis factor α, interferon γ, interleukin-5 and interleukin-13 levels in bronchoalveolar lavage fluid were quantified by commercial kits. The protein levels in pulmonary tissues were measured by Western blot analysis. Ghrelin ameliorated the histological pathology and airway hyperresponsiveness in the OVA-induced asthmatic mouse model. Consistently, OVA-increased total and differential leukocytes and levels of tumor necrosis factor α, interferon γ, interleukin-5 and interleukin-13 in bronchoalveolar lavage fluid were significantly attenuated by ghrelin. Ghrelin prevented the increased protein levels of the endoplasmic reticulum stress markers glucose regulated protein 78 and CCAAT/enhancer binding protein homologous protein and reversed the reduced levels of p-Akt in asthmatic mice. Ghrelin might prevent endoplasmic reticulum stress activation by stimulating the Akt signaling pathway, which attenuated inflammation and ameliorated asthma in mice. Ghrelin might be a new target for asthma therapy. Copyright © 2017. Published by Elsevier Inc.

Association of Urogenital Symptoms with History of Water Contact in Young Women in Areas Endemic for S. haematobium. A Cross-Sectional Study in Rural South Africa.

Science.gov (United States)

Galappaththi-Arachchige, Hashini Nilushika; Amlie Hegertun, Ingrid Elise; Holmen, Sigve; Qvigstad, Erik; Kleppa, Elisabeth; Sebitloane, Motshedisi; Ndhlovu, Patricia Doris; Vennervald, Birgitte Jyding; Gundersen, Svein Gunnar; Taylor, Myra; Kjetland, Eyrun Floerecke

2016-11-14

Female genital schistosomiasis is a neglected tropical disease caused by Schistosoma haematobium . Infected females may suffer from symptoms mimicking sexually transmitted infections. We explored if self-reported history of unsafe water contact could be used as a simple predictor of genital schistosomiasis. In a cross-sectional study in rural South Africa, 883 sexually active women aged 16-22 years were included. Questions were asked about urogenital symptoms and water contact history. Urine samples were tested for S. haematobium ova. A score based on self-reported water contact was calculated and the association with symptoms was explored while adjusting for other genital infections using multivariable logistic regression analyses. S. haematobium ova were detected in the urine of 30.5% of subjects. Having ova in the urine was associated with the water contact score ( p water contact included burning sensation in the genitals ( p = 0.005), spot bleeding ( p = 0.012), abnormal discharge smell ( p = 0.018), bloody discharge ( p = 0.020), genital ulcer ( p = 0.038), red urine ( p water contact was strongly associated with urogenital symptoms. In low-resource settings, a simple history including risk of water contact behaviour can serve as an indicator of urogenital schistosomiasis.

Experimental Design and Methods for Development of Diagnostic Assays for Schistosomiasis Using Monoclonal Antibodies.

Science.gov (United States)

1983-08-25

solium, Echinococcus granulosus , Entamoeba histolytica, or Wucher erTra-bancr--ofti. The S. mansoni glycoproteins that were immunoprecipitated by sera...Sera from patients or experimental animals infected with Schistosoma, Fasciola hepatica, Trichinella spiralis, Taenia solium, Echinococcus ... granulosus , or Paragonimus westermani cross-react in diag-nostic assays with antigens derived from schistosomes, whether as whole organisms (1-4), crude

coloproctectomie avec anastomose colo-sus-anale pour tumeur ...

African Journals Online (AJOL)

Une coloproctectomie fut réalisée le 30/06/2014 avec anastomose colo-anale, colostomie de protection sous-couvert d'une transfusion sanguine. L'examen histologique du segment colorectal prélevé objectiva une rectocolite granulomateuse autour de nombreux oeufs de schistosomes. En effet, le patient a vécu à Pahou, ...

Swimmer’s itch: etiology, impact, and risk factors in Europe

Czech Academy of Sciences Publication Activity Database

Soldánová, Miroslava; Selbach, C.; Kalbe, M.; Kostadinova, Aneta; Sures, B.

2013-01-01

Roč. 29, č. 2 (2013), s. 65-74 ISSN 1471-4922 R&D Projects: GA ČR GAP505/10/1562 Institutional support: RVO:60077344 Keywords : bird schistosomes * Trichobilharzia * swimmer's itch * Lymnaeidae * ecological factors * risk factors * Europe Subject RIV: EC - Immunology Impact factor: 6.217, year: 2013 http://www.sciencedirect.com/science/article/pii/S1471492212002000

Maternal Intake of Fish Oil but not of Linseed Oil Reduces the Antibody Response in Neonatal Mice

DEFF Research Database (Denmark)

Lauritzen, Lotte; Kjær, T. M. R.; Porsgaard, Trine

2011-01-01

Dietary levels of n-3 PUFA are believed to influence the immune system. The importance of the source of n-3 PUFA is debated. This study addressed how the content and source of n-3 PUFA in the maternal diet influenced tissue FA composition and the immune response to ovalbumin (OVA) in mice pups....... From the day of conception and throughout lactation, dams were fed diets containing 4% fat from linseed oil (LSO), fish oil (FO) or a n-3 PUFA-deficient diet (DEF). Pups were injected with OVA within 24 h of birth and sacrificed at weaning (day 21). Overall, the content of n-3 PUFA in milk, liver...

MOLECULAR APPROACH TO THE STUDY OF TREMATODE PARASITES : THE BLOOD FLUKE

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Philip T. LoVerde

2012-09-01

Full Text Available One important aspect of reproductive development in trematode parasites is the formation of a hardened eggshell which allows the zygote to develop into a miracidium in a hostile environment. The miracidium then can transfer the germline from the vertebrate host to snail intermediate host. Schistosome parasites, unlike other trematodes, have separate sexes and female reproductive development is known to depend on the presence of a male parasite. These facts make the blood flukes ideal material to study the mechanisms that underlie female reproductive development and eggshell formatian. We reasoned that the morphological and biochemical differences between the male and female must be reflected at the molecular level in the differential expression of sexually regulated genes. Radioactive single stranded cDNA was first transcribed from female RNA; and then sequences common to both male and female were removed by hybridization to an excess of male RNA. This probe was used to screen a cDNA library made from mRNA of adult worm paris. One hybridizing clone, pSMf 61-46, was shown to correspond to a 0.9 kilobase mRNA that is present only in mature female worms and is not detectable in female schistosomes from single-sex infections, in male worms or in eggs. Thus expression of the gene was female-specific. During normal bisexual infection this mRNA is first detected 28 days after infection (the time of worm pairing and increases to a high level at 35 days postinfection, coinciding with egg production. Thus the temporal expression of the gene was dependent on paining with male worm. The nucleotide sequence of the gene shows an open reading frame that encodes a 16 kDA polypeptide that shows strong homology with eggshell proteins on insects. A second female-specific cDNA clone, F-4, represents a 1.6 kilobase mRNA whose expression is also correlated with worm pairing and subsequent egg production, encodes a different putative eggshell component of 44 kDA. The

Comparison of anti-mullerian hormone and antral follicle count for assessment of ovarian reserve

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Sonal Panchal

2012-01-01

Full Text Available Aim: This study aims to compare the efficacy of AFC and AMH, as markers for ovarian reserve. Materials and Methods: 75 patients with PCO (polycystic ovaries undergoing IVF were randomized with 75 non-PCO patients. On day 3, volume of ovary was acquired, ovarian volume was defined by VOCAL, and Sono AVC was used to count the number of antral follicles. Sum total of antral follicles in both ovaries was taken as total antral follicle count (AFC. AMH was measured on the same day. Long agonist protocol with recombinant FSH (rFSH was used for IVF stimulation till at least two follicles of 18 mm were seen. hCG 10,000 iu was given and ovum pick up was done after 34-35 h. Primary end point was number of follicles >12 mm seen on day of hCG. Final end point was number of ova retrieved on ovum pick up. Correlation of AFC and AMH was checked for both end points and with each other. Results: Correlation of AFC and follicles >12 mm on day of hCG in PCO group is 0.56 and non-PCO group is 0.63, 1 and for AMH and follicles >12 mm on day of hCG in PCO group is 0.42 and non-PCO group is 0.47. Correlation of AFC with number of ova retrieved on OPU in PCO group is 0.44 and for non-PCO group is 0.50. The value for AMH is 0.39 in PCO and 0.43 for non-PCO group. Comparing correlation of AFC and AMH for primary end point in PCO group has ′z′ value 1.11(onetailed significance 0.1335, twotailed significance 0.267 and in non-PCO group comparison shows a ′z′ value of 1.39 (one tailed significance 0.0823, two-tailed significance 0.1645. Therefore in both groups, AFC and AMH correlates with total number of follicles >12 mm on day of hCG, but both AFC and AMH have independent significance. Comparing correlation of AFC and AMH with number of ova retrieved on OPU, in non-PCO group has ′z′ value of 0.54(one tailed 0.2946, two-tailed 0. 5892. In PCO group, this comparison shows, ′z′ value of 0.36(one tailed 0.3594, two tailed 0.7188. Conclusion: AFC and AMH

Polymorphic microsatellites in the human bloodfluke, Schistosoma japonicum, identified using a genomic resource

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Spear Robert

2011-02-01

Full Text Available Abstract Re-emergence of schistosomiasis in regions of China where control programs have ceased requires development of molecular-genetic tools to track gene flow and assess genetic diversity of Schistosoma populations. We identified many microsatellite loci in the draft genome of Schistosoma japonicum using defined search criteria and selected a subset for further analysis. From an initial panel of 50 loci, 20 new microsatellites were selected for eventual optimization and application to a panel of worms from endemic areas. All but one of the selected microsatellites contain simple tri-nucleotide repeats. Moderate to high levels of polymorphism were detected. Numbers of alleles ranged from 6 to 14 and observed heterozygosity was always >0.6. The loci reported here will facilitate high resolution population-genetic studies on schistosomes in re-emergent foci.

Squamous metaplasia as a manifestation of urogenital schistosomiasis and its complications

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A. Yu. Kolmakov

2016-01-01

Full Text Available Background. Leukoplakia or squamous metaplasia (SM of the bladder detect with the endoscopic diagnostic with urothelial biopsy. The reason for the development of SM, besides irritation of a mucous membrane by chemical reagents or drugs, is prolonged exposure of schistosome eggs (Schistosoma haematobium, penetrating into the bladder during invasion. The most common cause of urothelial SM is urogenital schistosomiasis (US and one of the most known and dangerous its complications is schistosomiasis bladder cancer (sBC. Features of cellular mechanisms linking the schistosomes invasion with the development of sBC are not well studied. Urothelial SM use to indicate by the presence of cancerous transformation, or may be a marker of long-term inflammation. The flow of squamous cell carcinoma of the bladder usually is accompanied by a keratinizing SM. Taking into account the socio-political conditions of the modern world and the development of tourism, the relevance of the diagnosis and treatment of patients with those diseases continues to grow. Materials and methods. The results of observation the group of 181 residents of the Republic of Angola with gross haematuria analyzed from 2009 till 2010. US verified in all cases. We conducted urine tests for detection of schistosomes, cytological examination of urine sediment (CEUS, ultrasound and endoscopic diagnostic methods, biopsy of the urothelium. The database of the hospitals used in the statistical analysis.Results. In 142 (78.5 % cases uncomplicated US confirmed, at 39 (21.5 % patients sBC revealed. Schistosomes invasion and trichomonas were combined in 21 (14.8 % cases. Changes and thickness of the bladder wall by ultrasound were accompanied with the SM in 26.8 % cases. The combination of SM and hydronephrosis caused by ureteral stenosis due to US were founded in 2 (1.4 % cases. The coincidence cases of PM with ultrasound picture, featuring for manifestations US did not exceed 14

Role of IL-4 receptor α-positive CD4(+) T cells in chronic airway hyperresponsiveness.

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Kirstein, Frank; Nieuwenhuizen, Natalie E; Jayakumar, Jaisubash; Horsnell, William G C; Brombacher, Frank

2016-06-01

TH2 cells and their cytokines are associated with allergic asthma in human subjects and with mouse models of allergic airway disease. IL-4 signaling through the IL-4 receptor α (IL-4Rα) chain on CD4(+) T cells leads to TH2 cell differentiation in vitro, implying that IL-4Rα-responsive CD4(+) T cells are critical for the induction of allergic asthma. However, mechanisms regulating acute and chronic allergen-specific TH2 responses in vivo remain incompletely understood. This study defines the requirements for IL-4Rα-responsive CD4(+) T cells and the IL-4Rα ligands IL-4 and IL-13 in the development of allergen-specific TH2 responses during the onset and chronic phase of experimental allergic airway disease. Development of acute and chronic ovalbumin (OVA)-induced allergic asthma was assessed weekly in CD4(+) T cell-specific IL-4Rα-deficient BALB/c mice (Lck(cre)IL-4Rα(-/lox)) and respective control mice in the presence or absence of IL-4 or IL-13. During acute allergic airway disease, IL-4 deficiency did not prevent the onset of TH2 immune responses and OVA-induced airway hyperresponsiveness or goblet cell hyperplasia, irrespective of the presence or absence of IL-4Rα-responsive CD4(+) T cells. In contrast, deficiency of IL-13 prevented allergic asthma, irrespective of the presence or absence of IL-4Rα-responsive CD4(+) T cells. Importantly, chronic allergic inflammation and airway hyperresponsiveness were dependent on IL-4Rα-responsive CD4(+) T cells. Deficiency in IL-4Rα-responsive CD4(+) T cells resulted in increased numbers of IL-17-producing T cells and, consequently, increased airway neutrophilia. IL-4-responsive T helper cells are dispensable for acute OVA-induced airway disease but crucial in maintaining chronic asthmatic pathology. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Effect of combined nitrogen dioxide and carbon nanoparticle exposure on lung function during ovalbumin sensitization in Brown Norway rat.

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Skander Layachi

Full Text Available The interaction of particulate and gaseous pollutants in their effects on the severity of allergic inflammation and airway responsiveness are not well understood. We assessed the effect of exposure to NO(2 in the presence or absence of repetitive treatment with carbon nanoparticle (CNP during allergen sensitization and challenges in Brown-Norway (BN rat, in order to assess their interactions on lung function and airway responses (AR to allergen and methacholine (MCH, end-expiratory lung volume (EELV, bronchoalveolar lavage fluid (BALF cellular content, serum and BALF cytokine levels and histological changes. Animals were divided into the following groups (n = 6: Control; CNP (Degussa-FW2: 13 nm, 0.5 mg/kg instilled intratracheally ×3 at 7-day intervals; OVA: ovalbumin-sensitised; OVA+CNP: both sensitized and exposed to CNP. Rats were divided into equal groups exposed either to air or to NO(2, 10 ppm, 6 h/d, 5d/wk for 4 weeks. Exposure to NO(2, significantly enhanced lung inflammation and airway reactivity, with a significantly larger effect in animals sensitized to allergen, which was related to a higher expression of TH1 and TH2-type cytokines. Conversely, exposure to NO(2 in animals undergoing repeated tracheal instillation of CNP alone, increased BALF neutrophilia and enhanced the expression of TH1 cytokines: TNF-α and IFN-γ, but did not show an additive effect on airway reactivity in comparison to NO(2 alone. The exposure to NO(2 combined with CNP treatment and allergen sensitization however, unexpectedly resulted in a significant decrease in both airway reactivity to allergen and to methacholine, and a reduction in TH2-type cytokines compared to allergen sensitization alone. EELV was significantly reduced with sensitization, CNP treatment or both. These data suggest an immunomodulatory effect of repeated tracheal instillation of CNP on the proinflammatory effects of NO(2 exposure in sensitized BN rat. Furthermore, our findings suggest

A color-coded reporter model to study the effect of immunosuppressants on CD8+ T-cell memory in antitumor and alloimmune responses.

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Rovira, Jordi; Sabet-Baktach, Manije; Eggenhofer, Elke; Lantow, Margareta; Koehl, Gudrun E; Schlitt, Hans J; Campistol, Josep M; Geissler, Edward K; Kroemer, Alexander

2013-01-15

Mammalian target of rapamycin (mTOR) inhibitors possess anticancer properties potentially useful in reducing posttransplantation malignancy. Besides controlling tumor-sensitive proliferative and angiogenic effects, mTOR influences transcription factors T-bet and Eomesodermin (Eomes) in CD8 cytotoxic T cells (Tc), which are key in rejecting tumors, and allografts. To study the role of mTOR in tumor and transplant immunity in an antigen-specific way, we used T-cell receptor transgenic B6.OTI recipients, B6.OVA.TG donors, and OVA-B16F10 melanoma cells. For tracking color-coded OTI-Tc cells associated with antitumor and alloimmunity in vivo, CD8-OTI transgenic reporter mice were created by crossbreeding DsRed-expressing B6.Nagy mice with B6.OTI mice. The role of mTOR in regulating the differentiation and function of alloreactive Tc cells in vitro was explored by stimulating OTI-Tc cells with ovalbumin-transgenic antigen-presenting cells in the presence of rapamycin or tacrolimus. Rapamycin, but not tacrolimus, induced a pro-antitumor phenotypic shift from CD62LCD44 effector memory Tc cells to CD62LCD44 central memory Tc cells, which featured up-regulated levels of T-bet and Eomes and preserved levels of interferon-γ and perforin. For future investigations, an in vivo model was established whereby DsRedOTI-Tc cells adoptively transferred into B6 mice bearing either a ovalbumin-transgenic mouse skin transplant or OVA-B16F10 tumor could be traced by fluorescence-activated cell sorting analysis as effector or memory Tc cells in transplant and tumor tissues. mTOR, but not calcineurin, inhibition spares antitumoral memory Tc cells by distinctively regulating T-bet and Eomes. This finding is now testable in a new tumor transplant model, which incorporates DsRedOTI-Tc cell tracing, opening the way to study the differential effects of immunosuppressants in posttransplantation malignancy.

Self-assembling nanoparticles containing dexamethasone as a novel therapy in allergic airways inflammation.

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Nicholas J Kenyon

Full Text Available Nanocarriers can deliver a wide variety of drugs, target them to sites of interest, and protect them from degradation and inactivation by the body. They have the capacity to improve drug action and decrease undesirable systemic effects. We have previously developed a well-defined non-toxic PEG-dendritic block telodendrimer for successful delivery of chemotherapeutics agents and, in these studies, we apply this technology for therapeutic development in asthma. In these proof-of-concept experiments, we hypothesized that dexamethasone contained in self-assembling nanoparticles (Dex-NP and delivered systemically would target the lung and decrease allergic lung inflammation and airways hyper-responsiveness to a greater degree than equivalent doses of dexamethasone (Dex alone. We found that ovalbumin (Ova-exposed mice treated with Dex-NP had significantly fewer total cells (2.78 ± 0.44 × 10(5 (n = 18 vs. 5.98 ± 1.3 × 10(5 (n = 13, P<0.05 and eosinophils (1.09 ± 0.28 × 10(5 (n = 18 vs. 2.94 ± 0.6 × 10(5 (n = 12, p<0.05 in the lung lavage than Ova-exposed mice alone. Also, lower levels of the inflammatory cytokines IL-4 (3.43 ± 1.2 (n = 11 vs. 8.56 ± 2.1 (n = 8 pg/ml, p<0.05 and MCP-1 (13.1 ± 3.6 (n = 8 vs. 28.8 ± 8.7 (n = 10 pg/ml, p<0.05 were found in lungs of the Dex-NP compared to control, and they were not lower in the Dex alone group. In addition, respiratory system resistance was lower in the Dex-NP compared to the other Ova-exposed groups suggesting a better therapeutic effect on airways hyperresponsiveness. Taken together, these findings from early-stage drug development studies suggest that the encapsulation and protection of anti-inflammatory agents such as corticosteroids in nanoparticle formulations can improve efficacy. Further development of novel drugs in nanoparticles is warranted to explore potential treatments for chronic inflammatory diseases such as asthma.

Th cells promote CTL survival and memory via acquired pMHC-I and endogenous IL-2 and CD40L signaling and by modulating apoptosis-controlling pathways.

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Channakeshava Sokke Umeshappa

Full Text Available Involvement of CD4(+ helper T (Th cells is crucial for CD8(+ cytotoxic T lymphocyte (CTL-mediated immunity. However, CD4(+ Th's signals that govern CTL survival and functional memory are still not completely understood. In this study, we assessed the role of CD4(+ Th cells with acquired antigen-presenting machineries in determining CTL fates. We utilized an adoptive co-transfer into CD4(+ T cell-sufficient or -deficient mice of OTI CTLs and OTII Th cells or Th cells with various gene deficiencies pre-stimulated in vitro by ovalbumin (OVA-pulsed dendritic cell (DCova. CTL survival was kinetically assessed in these mice using FITC-anti-CD8 and PE-H-2K(b/OVA257-264 tetramer staining by flow cytometry. We show that by acting via endogenous CD40L and IL-2, and acquired peptide-MHC-I (pMHC-I complex signaling, CD4(+ Th cells enhance survival of transferred effector CTLs and their differentiation into the functional memory CTLs capable of protecting against highly-metastasizing tumor challenge. Moreover, RT-PCR, flow cytometry and Western blot analysis demonstrate that increased survival of CD4(+ Th cell-helped CTLs is matched with enhanced Akt1/NF-κB activation, down-regulation of TRAIL, and altered expression profiles with up-regulation of prosurvival (Bcl-2 and down-regulation of proapoptotic (Bcl-10, Casp-3, Casp-4, Casp-7 molecules. Taken together, our results reveal a previously unexplored mechanistic role for CD4(+ Th cells in programming CTL survival and memory recall responses. This knowledge could also aid in the development of efficient adoptive CTL cancer therapy.

Th cells promote CTL survival and memory via acquired pMHC-I and endogenous IL-2 and CD40L signaling and by modulating apoptosis-controlling pathways.

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Umeshappa, Channakeshava Sokke; Xie, Yufeng; Xu, Shulin; Nanjundappa, Roopa Hebbandi; Freywald, Andrew; Deng, Yulin; Ma, Hong; Xiang, Jim

2013-01-01

Involvement of CD4(+) helper T (Th) cells is crucial for CD8(+) cytotoxic T lymphocyte (CTL)-mediated immunity. However, CD4(+) Th's signals that govern CTL survival and functional memory are still not completely understood. In this study, we assessed the role of CD4(+) Th cells with acquired antigen-presenting machineries in determining CTL fates. We utilized an adoptive co-transfer into CD4(+) T cell-sufficient or -deficient mice of OTI CTLs and OTII Th cells or Th cells with various gene deficiencies pre-stimulated in vitro by ovalbumin (OVA)-pulsed dendritic cell (DCova). CTL survival was kinetically assessed in these mice using FITC-anti-CD8 and PE-H-2K(b)/OVA257-264 tetramer staining by flow cytometry. We show that by acting via endogenous CD40L and IL-2, and acquired peptide-MHC-I (pMHC-I) complex signaling, CD4(+) Th cells enhance survival of transferred effector CTLs and their differentiation into the functional memory CTLs capable of protecting against highly-metastasizing tumor challenge. Moreover, RT-PCR, flow cytometry and Western blot analysis demonstrate that increased survival of CD4(+) Th cell-helped CTLs is matched with enhanced Akt1/NF-κB activation, down-regulation of TRAIL, and altered expression profiles with up-regulation of prosurvival (Bcl-2) and down-regulation of proapoptotic (Bcl-10, Casp-3, Casp-4, Casp-7) molecules. Taken together, our results reveal a previously unexplored mechanistic role for CD4(+) Th cells in programming CTL survival and memory recall responses. This knowledge could also aid in the development of efficient adoptive CTL cancer therapy.

Counterbalancing of TH2-driven allergic airway inflammation by IL-12 does not require IL-10.

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Tournoy, K G; Kips, J C; Pauwels, R A

2001-03-01

Asthma is characterized by allergen-induced airway inflammation orchestrated by TH2 cells. The TH1-promoting cytokine IL-12 is capable of inhibiting the TH2-driven allergen-induced airway changes in mice and is therefore regarded as an interesting strategy for treating asthma. The antiallergic effects of IL-12 are only partially dependent of IFN-gamma. Because IL-12 is a potent inducer of the anti-inflammatory cytokine IL-10, the aim of the present study was to investigate in vivo whether the antiallergic effects of IL-12 are mediated through IL-10. C57BL/6J-IL-10 knock-out (IL-10(-/-)) mice were sensitized intraperitoneally to ovalbumin (OVA) and subsequently exposed from day 14 to day 21 to aerosolized OVA (1%). IL-12 was administered intraperitoneally during sensitization, subsequent OVA exposure, or both. IL-12 inhibited the OVA-induced airway eosinophilia, despite the absence of IL-10. Moreover, a shift from a TH2 inflammatory pattern toward a TH1 reaction was observed, with concomitant pronounced mononuclear peribronchial inflammation after IL-12 treatment. Allergen-specific IgE synthesis was completely suppressed only when IL-12 was administered along with the allergen sensitization. Furthermore, treating the animals with IL-12 at the time of the secondary allergen challenge resulted not only in a significant suppression of the airway responsiveness but also in an important IFN-gamma-associated toxicity. These results indicate that IL-12 is able to inhibit allergen-induced airway changes, even in the absence of IL-10. In addition, our results raise concerns regarding the redirection of TH2 inflammation by TH1-inducing therapies because treatment with IL-12 resulted not only in a disappearance of the TH2 inflammation but also in a TH1-driven inflammatory pulmonary pathology.