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Find video protocols related to scientific articles indexed in Pubmed.
Optimization of multicore fiber for high-temperature sensing.
Opt Lett
PUBLISHED: 08-15-2014
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We demonstrate a novel high-temperature sensor using multicore fiber (MCF) spliced between two single-mode fibers. Launching light into such fiber chains creates a supermode interference pattern in the MCF that translates into a periodic modulation in the transmission spectrum. The spectrum shifts with changes in temperature and can be easily monitored in real time. This device is simple to fabricate and has been experimentally shown to operate at temperatures up to 1000°C in a very stable manner. Through simulation, we have optimized the multicore fiber design for sharp spectral features and high overall transmission in the optical communications window. Comparison between the experiment and the simulation has also allowed determination of the thermo-optic coefficient of the MCF as a function of temperature.
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Heritability of phenotypes associated with glucose homeostasis and adiposity in a rural area of Brazil.
Ann. Hum. Genet.
PUBLISHED: 08-02-2014
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We aimed to estimate the heritability and genetic correlation between glucose homeostasis and adiposity traits in a population in a rural community in Brazil. The Jequitinhonha Community Family Study cohort consists of subjects aged ?18 years residing in rural areas in Brazil. The data on the following traits were assembled for 280 individuals (51.7% women): body mass index (BMI), body fat percentage, waist and mid-upper arm circumferences, triceps skinfold, conicity index, insulin, glucose, high-density lipoprotein cholesterol (HDLc), triglycerides and C-reactive protein. Extended pedigrees were constructed up to the third generation of individuals using the data management software PEDSYS. The heritability and genetic correlations were estimated using a variance component method. The age- and sex-adjusted heritability values estimated for insulin (h(2) = 52%), glucose (h(2) = 51%), HDLc (h(2) = 58%), and waist circumference (WC; h(2) = 49%) were high. Significantly adjusted genetic correlations were observed between insulin paired with each of the following phenotypes; (BMI; ?g = 0.48), WC (?g = 0.47) and HDLc (?g = -0.47). The homeostasis model assessment of insulin resistance (HOMA-IR) was genetically correlated with BMI (?g = 0.53) and HDLc (?g = -0.58). The adjusted genetic correlations between traits were consistently higher compared with the environmental correlations. In conclusion, glucose metabolism and adiposity traits are highly heritable and share common genetic effects with body adiposity traits.
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Multicore fiber sensor for high-temperature applications up to 1000°C.
Opt Lett
PUBLISHED: 08-01-2014
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A novel high temperature sensor based on customized multicore fiber (MCF) is proposed and experimentally demonstrated. The sensor consists of a short, few-centimeter-long segment of MCF spliced between two standard single-mode fibers. Due to interference effects, the transmission spectrum through this fiber chain features sharp and deep notches. Exposing the MCF segment to increasing temperatures of up to 1000°C results in a shift of the transmission notches toward longer wavelengths with a slope of approximately 29??pm/°C at lower temperatures and 52??pm/°C at higher temperatures, enabling temperature measurements with high sensitivity and accuracy. Due to its compact size and mechanical rigidity, the MCF sensor can be subjected to harsh environments. The fabrication of the MCF sensor is straightforward and reproducible, making it an inexpensive fiber device.
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Antiparasitic activities of novel ruthenium/lapachol complexes.
J. Inorg. Biochem.
PUBLISHED: 03-19-2014
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The present study describes the synthesis, characterization, antileishmanial and antiplasmodial activities of novel diimine/(2,2'-bipyridine (bipy), 1,10-phenanthroline (phen), 4,4'-methylbipyridine (Me-bipy) and 4,4'-methoxybipyridine (MeO-bipy)/phosphine/ruthenium(II) complexes containing lapachol (Lap, 2-hydroxy-3-(3-33 methyl-2-buthenyl)-1,4-naphthoquinone) as bidentate ligand. The [Ru(Lap)(PPh3)2(bipy)]PF6 (1), [Ru(Lap)(PPh3)2(Me-bipy)]PF6 (2), [Ru(Lap)(PPh3)2(MeO-bipy)]PF6(3) and[Ru(Lap)(PPh3)2(phen)]PF6 (4) complexes, PPh3=triphenylphospine, were synthesized from the reactions of cis-[RuCl2(PPh3)2(X-bipy)] or cis-[RuCl2(PPh3)2(phen)], with lapachol. The [RuCl2(Lap)(dppb)] (5) [dppb=1,4-bis(diphenylphosphine)butane] was synthesized from the mer-[RuCl3(dppb)(H2O)] complex. The complexes were characterized by elemental analysis, molar conductivity, infrared and UV-vis spectroscopy, (31)P{(1)H} and (1)H NMR, and cyclic voltammetry. The Ru(III) complex, [RuCl2(Lap)(dppb)], was also characterized by the EPR technique. The structure of the complexes [Ru(Lap)(PPh3)2(bipy)]PF6 and [RuCl2(Lap)(dppb)] was elucidated by X-ray diffraction. The evaluation of the antiparasitic activities of the complexes against Leishmania amazonensis and Plasmodium falciparum demonstrated that lapachol-ruthenium complexes are more potent than the free lapachol. The [RuCl2(Lap)(dppb)] complex is the most potent and selective antiparasitic compound among the five new ruthenium complexes studied in this work, exhibiting an activity comparable to the reference drugs.
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An immunomics approach to schistosome antigen discovery: antibody signatures of naturally resistant and chronically infected individuals from endemic areas.
PLoS Pathog.
PUBLISHED: 03-01-2014
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Schistosomiasis is a neglected tropical disease that is responsible for almost 300,000 deaths annually. Mass drug administration (MDA) is used worldwide for the control of schistosomiasis, but chemotherapy fails to prevent reinfection with schistosomes, so MDA alone is not sufficient to eliminate the disease, and a prophylactic vaccine is required. Herein, we take advantage of recent advances in systems biology and longitudinal studies in schistosomiasis endemic areas in Brazil to pilot an immunomics approach to the discovery of schistosomiasis vaccine antigens. We selected mostly surface-derived proteins, produced them using an in vitro rapid translation system and then printed them to generate the first protein microarray for a multi-cellular pathogen. Using well-established Brazilian cohorts of putatively resistant (PR) and chronically infected (CI) individuals stratified by the intensity of their S. mansoni infection, we probed arrays for IgG subclass and IgE responses to these antigens to detect antibody signatures that were reflective of protective vs. non-protective immune responses. Moreover, probing for IgE responses allowed us to identify antigens that might induce potentially deleterious hypersensitivity responses if used as subunit vaccines in endemic populations. Using multi-dimensional cluster analysis we showed that PR individuals mounted a distinct and robust IgG1 response to a small set of newly discovered and well-characterized surface (tegument) antigens in contrast to CI individuals who mounted strong IgE and IgG4 responses to many antigens. Herein, we show the utility of a vaccinomics approach that profiles antibody responses of resistant individuals in a high-throughput multiplex approach for the identification of several potentially protective and safe schistosomiasis vaccine antigens.
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Serological screening of the Schistosoma mansoni adult worm proteome.
PLoS Negl Trop Dis
PUBLISHED: 03-01-2014
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New interventions tools are a priority for schistosomiasis control and elimination, as the disease is still highly prevalent. The identification of proteins associated with active infection and protective immune response may constitute the basis for the development of a successful vaccine and could also indicate new diagnostic candidates. In this context, post-genomic technologies have been progressing, resulting in a more rational discovery of new biomarkers of resistance and antigens for diagnosis.
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Profile of natural killer cells after a previous natural Vaccinia virus infection in an in vitro viral re-exposure.
Virus Res.
PUBLISHED: 02-03-2014
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The present study compares the profile of NK cells in an in vitro re-exposure by Vaccinia virus (VACV), in groups that have had a previous vaccination or natural infection. Our data suggests that stimulation with VACV triggers a cytotoxic response by NK cells marked by an increase of NCRs: NKp30, NKp44, and NKp46 in infected (vaccinated and unvaccinated) subjects and in non-infected vaccinated patients, when compared with non-infected unvaccinated individuals. However, the degranulation and secretion processes are inhibited in infected (vaccinated and unvaccinated) subjects and in the non-infected vaccinated patients, when compared with non-infected unvaccinated individuals. We demonstrated that stimulation with VACV downregulates the percentage of expression of Perforin, Granzyme A, and CD107a, but upregulate CD94 in infected (vaccinated and unvaccinated) subjects and in non-infected vaccinated patients, when compared with non-infected unvaccinated individuals. Furthermore, the percentage of IFN-?(+) NK cells was significantly lower in non-infected unvaccinated subjects, when compared with infected (vaccinated and unvaccinated) and non-infected vaccinated individuals. Our results also show that the percentage of TNF-?(+) NK cells was significantly higher in infected (vaccinated and unvaccinated) subjects and in non-infected vaccinated patients, when compared with non-infected unvaccinated individuals, after in vitro stimulation with UV-inactivated VACV. Our data suggest that the expression of NCRs NKp30, NKp44, NKp46 and cytokines by NK cells are important in the innate response against VACV.
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Immunological profile of resistance and susceptibility in naturally infected dogs by Leishmania infantum.
Vet. Parasitol.
PUBLISHED: 01-23-2014
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Visceral leishmaniasis has a great impact on public health, and dogs are considered the main domestic reservoir of Leishmania infantum, the causal parasite. In this study, 159 animals naturally infected by L. infantum from an endemic area of Brazil were evaluated through an analysis of cellular responses, using flow cytometry, and of the hematological parameters. The results confirmed that disease progression is associated with anemia and reductions in eosinophils, monocytes and lymphocytes. The investigation of the immune response, based on the immunophenotypic profile of peripheral blood, showed declines in the absolute numbers of T lymphocytes CD5(+) and their subsets (CD4(+) and CD8(+)) and a drop of B lymphocytes in asymptomatic seropositive (AD-II) and symptomatic seropositive (SD) dogs. Neutrophils, when stimulated with soluble antigen of L. infantum, showed higher synthesis of interferon (IFN)-?(+) in AD-II and SD groups, with decreased production of interleukin (IL)-4(+) in asymptomatic seronegative dogs positive for L. infantum infection based on polymerase chain reaction testing (AD-I group). In the AD-II and SD groups, subpopulations of stimulated lymphocytes (CD4(+) and CD8(+)) also exhibited greater synthesis of IFN-?(+) and IL-4(+) in culture. These results suggest that the animals of the AD-II and SD groups exhibited a mixed immune response (Type 1 and 2) and the AD-I group presenting an immune profile very similar to normal control animals.
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LBSapSal-vaccinated dogs exhibit increased circulating T-lymphocyte subsets (CD4? and CD8?) as well as a reduction of parasitism after challenge with Leishmania infantum plus salivary gland of Lutzomyia longipalpis.
Parasit Vectors
PUBLISHED: 01-18-2014
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The development of a protective vaccine against canine visceral leishmaniasis (CVL) is an alternative approach for interrupting the domestic cycle of Leishmania infantum. Given the importance of sand fly salivary proteins as potent immunogens obligatorily co-deposited during transmission of Leishmania parasites, their inclusion in an anti-Leishmania vaccine has been investigated in the last few decades. In this context, we previously immunized dogs with a vaccine composed of L. braziliensis antigens plus saponin as the adjuvant and sand fly salivary gland extract (LBSapSal vaccine). This vaccine elicited an increase in both anti-saliva and anti-Leishmania IgG isotypes, higher counts of specific circulating CD8? T cells, and high NO production.
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Evaluation of change in canine diagnosis protocol adopted by the visceral leishmaniasis control program in Brazil and a new proposal for diagnosis.
PLoS ONE
PUBLISHED: 01-01-2014
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The techniques used for diagnosis of canine visceral leishmaniasis (CVL) in Brazil ELISA and IFAT have been extensively questioned because of the accuracy of these tests. A recent change in the diagnosis protocol excluded IFAT and included the Dual-Path Platform (DPP). We evaluated the prevalence and incidence rates of Leishmania spp. before and after the change in the protocol. In addition, based on our results, we propose a new alternative that is less expensive for the screening and confirmation of CVL. Plasma samples were obtained from a serobank from dogs evaluated in a cross-sectional study (1,226 dogs) and in a cohort study of susceptible animals (n = 447), followed for 26 months. Serology testing was performed using ELISA, IFAT, and DPP. The incidence and prevalence of CVL were determined by using the protocol of the Visceral Leishmaniasis Control and Surveillance Program until 2012 (ELISA and IFAT using filter paper) and the protocol used after 2012 (DPP and ELISA using plasma). The prevalence was 6.2% and the incidence was 2.8 per 1,000 dog-months for the protocol used until 2012. For the new diagnosis protocol for CVL resulted in an incidence of 5.4 per 1,000 dog-months and a prevalence of 8.1%. Our results showed that the prevalence and incidence of infection were far greater than suggested by the previously used protocol and that the magnitude of infection in endemic areas has been underestimated. As tests are performed sequentially and euthanasia of dogs is carried out when the serological results are positive in both tests, the sequence does not affect the number of animals to be eliminated by the Control Program. Then we suggest to municipalities with a large demand of exams to use ELISA for screening and DPP for confirmation, since this allows easier performance and reduced cost.
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Plasma cytokine expression is associated with cardiac morbidity in chagas disease.
PLoS ONE
PUBLISHED: 01-01-2014
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The expression of immune response appears to be associated with morbidity in Chagas disease. However, the studies in this field have usually employed small samples of patients and statistical analyses that do not consider the wide dispersion of cytokine production observed in these patients. The aim of this study was to evaluate the plasma cytokine levels in well-defined clinical polar groups of chagasic patients divided into categories that better reflect the wide cytokine profile and its relationship with morbidity. Patients infected with Trypanosoma cruzi (T. cruzi) were grouped as indeterminate (IND) and cardiac (CARD) forms ranging from 23 to 69 years of age (mean of 45.6±11.25). The IND group included 82 individuals, ranging from 24 to 66 years of age (mean of 39.6±10.3). The CARD group included 94 patients ranging from 23 to 69 years of age (mean of 48±12.52) presenting dilated cardiomyopathy. None of the patients have undergone chemotherapeutic treatment, nor had been previously treated for T. cruzi infection. Healthy non-chagasic individuals, ranging from 29 to 55 years of age (mean of 42.6±8.8) were included as a control group (NI). IND patients have a higher intensity of interleukin 10 (IL-10) expression when compared with individuals in the other groups. By contrast, inflammatory cytokine expression, such as interferon gamma (IFN-?), tumor necrosis factor alpha (TNF-?), interleukin 6 (IL-6), and interleukin 1 beta (IL-1?), proved to be the highest in the CARD group. Correlation analysis showed that higher IL-10 expression was associated with better cardiac function, as determined by left ventricular ejection fraction and left ventricular diastolic diameter values. Altogether, these findings reinforce the concept that a fine balance between regulatory and inflammatory cytokines represents a key element in the establishment of distinct forms of chronic Chagas disease.
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Longitudinal analysis of antigen specific response in individuals with Schistosoma mansoni infection in an endemic area of Minas Gerais, Brazil.
Trans. R. Soc. Trop. Med. Hyg.
PUBLISHED: 11-04-2013
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Immunoepidemiologic studies have shown a relationship between IgE and IgG4 antibodies with age and with resistance and susceptibility to infection. It is believed that the IgE and IgG4 responses to soluble egg antigen (SEA) can be used for serological analysis of infection and post-treatment status. This study aimed to evaluate the association between Schistosoma mansoni infection and anti-SEA IgG4 and IgE reactivities, and determine whether these reactivities could be used as biomarkers of infection.
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Unprecedented carbon accumulation in mined soils: the synergistic effect of resource input and plant species invasion.
Ecol Appl
PUBLISHED: 10-24-2013
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Opencast mining causes severe impacts on natural environments, often resulting in permanent damage to soils and vegetation. In the present study we use a 14-year restoration chronosequence to investigate how resource input and spontaneous plant colonization promote the revegetation and reconstruction of mined soils in central Brazil. Using a multi-proxy approach, combining vegetation surveys with the analysis of plant and soil isotopic abundances (delta13C and delta15N) and chemical and physical fractionation of organic matter in soil profiles, we show that: (1) after several decades without vegetation cover, the input of nutrient-rich biosolids into exposed regoliths prompted the establishment of a diverse plant community (> 30 species); (2) the synergistic effect of resource input and plant colonization yielded unprecedented increases in soil carbon, accumulating as chemically stable compounds in occluded physical fractions and reaching much higher levels than observed in undisturbed ecosystems; and (3) invasive grasses progressively excluded native species, limiting nutrient availability, but contributing more than 65% of the total accumulated soil organic carbon. These results show that soil-plant feedbacks regulate the amount of available resources, determining successional trajectories and alternative stable equilibria in degraded areas undergoing restoration. External inputs promote plant colonization, soil formation, and carbon sequestration, at the cost of excluding native species. The introduction of native woody species would suppress invasive grasses and increase nutrient availability, bringing the system closer to its original state. However, it is difficult to predict whether soil carbon levels could be maintained without the exotic grass cover. We discuss theoretical and practical implications of these findings, describing how the combination of resource manipulation and management of invasive species could be used to optimize restoration strategies, counteracting soil degradation while maintaining species diversity.
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Matrix metalloproteinases 2 and 9 are differentially expressed in patients with indeterminate and cardiac clinical forms of Chagas disease.
Infect. Immun.
PUBLISHED: 07-15-2013
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Dilated chronic cardiomyopathy (DCC) from Chagas disease is associated with myocardial remodeling and interstitial fibrosis, resulting in extracellular matrix (ECM) changes. In this study, we characterized for the first time the serum matrix metalloproteinase 2 (MMP-2) and MMP-9 levels, as well as their main cell sources in peripheral blood mononuclear cells from patients presenting with the indeterminate (IND) or cardiac (CARD) clinical form of Chagas disease. Our results showed that serum levels of MMP-9 are associated with the severity of Chagas disease. The analysis of MMP production by T lymphocytes showed that CD8(+) T cells are the main mononuclear leukocyte source of both MMP-2 and MMP-9 molecules. Using a new 3-dimensional model of fibrosis, we observed that sera from patients with Chagas disease induced an increase in the extracellular matrix components in cardiac spheroids. Furthermore, MMP-2 and MMP-9 showed different correlations with matrix proteins and inflammatory cytokines in patients with Chagas disease. Our results suggest that MMP-2 and MMP-9 show distinct activities in Chagas disease pathogenesis. While MMP-9 seems to be involved in the inflammation and cardiac remodeling of Chagas disease, MMP-2 does not correlate with inflammatory molecules.
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Analysis using canine peripheral blood for establishing in vitro conditions for monocyte differentiation into macrophages for Leishmania chagasi infection and T-cell subset purification.
Vet. Parasitol.
PUBLISHED: 07-11-2013
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Canine visceral leishmaniasis (CVL) is a parasitic disease endemic in many countries, and dogs present as the major natural reservoir of the parasite, Leishmania chagasi (syn. L. infantum). Biomarkers in the canine immune system is an important technique in the course of developing vaccines and treatment strategies against CVL. New methodologies for studying the immune response of dogs during Leishmania infection and after receiving vaccines and treatments against CVL would be useful. In this context, we used peripheral blood mononuclear cells (PBMCs) from healthy dogs to evaluate procedures related to (i) establishment of in vitro conditions of monocytes differentiated into macrophages infected with L. chagasi and (ii) purification procedures of T-cell subsets (CD4(+) and CD8(+)) using microbeads. Our data demonstrated that after 5 days of differentiation, macrophages were able to induce significant phagocytic and microbicidal activity after L. chagasi infection and also showed increased frequency of parasitism and a higher parasite load. Although N-acetyl-?-d-glucosaminidase (NAG) levels presented similar levels of macrophage culture and L. chagasi infection, a progressive decrease in myeloperoxidase (MPO) levels was a hallmark over 5 days of culture. High purity levels (>90%) of CD4 and CD8 T cells were obtained on a magnetic separation column. We concluded that monocytes differentiated into macrophages at 5 days and displayed an intermediate frequency of parasitism and parasite load 72 h after L. chagasi infection. Furthermore, the purification system using canine T-lymphocyte subsets obtained after 5 days of monocyte differentiation proved efficient for CD4 or CD8 T-cell purification (?90%). The in vitro analysis using L. chagasi-infected macrophages and purified T cells presented a prospective methodology that could be incorporated in CVL vaccine and treatment studies that aim to analyze the microbicidal potential induced by specific CD4(+) and/or CD8(+) T cells.
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Cellular immunophenotypic profile in the splenic compartment during canine visceral leishmaniasis.
Vet. Immunol. Immunopathol.
PUBLISHED: 06-23-2013
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To determine the role of the spleen in the pathogenesis of canine visceral leishmaniasis (CVL), we analyzed cellular immunophenotypic profiles of 52 dogs naturally infected with Leishmania infantum, clinically classified as follows: asymptomatic dogs-I (AD-I), seronegative/PCR+; asymptomatic dogs-II (AD-II), seropositive/PCR+; oligosymptomatic dogs (OD) and symptomatic dogs (SD). Seven non-infected dogs (CD) were included as a control group. AD-II presented higher levels of CD8+ T splenocytes and lower TCD4+/TCD8+ ratio in comparison with CD. OD and SD showed lower percentages of CD21+ as compared with AD-II. All seropositive dogs presented lower levels of CD45RA+ than CD. Regardless of the stimuli used, the proliferation index from splenocytes in vitro was inversely correlated with clinical status. After LSA stimulation, there was a higher percentage of specific CD8+ T in AD-II than CD and non-stimulated culture. In contrast, splenocytes from SD under in vitro LSA stimulation induced decreased MHC-II+ expression in comparison with all groups, and non-stimulated culture. In conclusion, the role of CD8+ T splenocytes seems to be important for an effective immunological response, a hallmark of asymptomatic CVL, whereas the pronounced loss of MHC-II expression upon LSA stimulation is a biomarker of symptomatic CVL.
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Inflammatory mediators from monocytes down-regulate cellular proliferation and enhance cytokines production in patients with polar clinical forms of Chagas disease.
Hum. Immunol.
PUBLISHED: 05-28-2013
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Exposure to Trypanosoma cruzi parasites induces monocytes and macrophages to produce various endogenous mediators, including prostaglandins and cytokines. To clarify the involvement of monocytes as an important source of inflammatory mediators in Chagas disease patients, we evaluated PBMC before and after depletion of adherent cells (monocytes) from patients with indeterminate (IND) and cardiac (CARD) clinical forms and from non-infected individuals (NI). We demonstrated that after the partial depletion of adherent cells, production of PGE2 was slightly decreased in patients with Chagas disease. Inhibition of the cells by indomethacin increased the proliferation in PBMC cells from patients after antigen stimulation. Pro-inflammatory cytokines as IL-2 and IFN-? also had a greater decrease after partial depletion of adherent cells in both clinical forms of Chagas disease. IL-10 and IL-5 levels were also reduced after partial depletion of adherent cells both in IND and CARD patients. In addition, we evaluated the APC potential of B cells and observed that the MHCII and CD80 molecules had an increased expression after partial depletion of most monocytes in all groups. Thus, inflammatory mediators produced by monocytes seem to be important to modulate immune responses in Chagas disease by regulating the processes of inflammation and antigen presentation.
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The Human Hookworm Vaccine.
Vaccine
PUBLISHED: 04-20-2013
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Hookworm infection is one of the worlds most common neglected tropical diseases and a leading cause of iron deficiency anemia in low- and middle-income countries. A Human Hookworm Vaccine is currently being developed by the Sabin Vaccine Institute and is in phase 1 clinical testing. The candidate vaccine is comprised of two recombinant antigens known as Na-GST-1 and Na-APR-1, each of which is an important parasite enzyme required for hookworms to successfully utilize host blood as a source of energy. The recombinant proteins are formulated on Alhydrogel(®) and are being tested in combination with a synthetic Toll-like receptor 4 agonist. The aim of the vaccine is to induce anti-enzyme antibodies that will reduce both host blood loss and the number of hookworms attached to the gut. Transfer of the manufacturing technology to the Oswaldo Cruz Foundation (FIOCRUZ)/Bio-Manguinhos (a Brazilian public sector developing country vaccine manufacturer) is planned, with a clinical development plan that could lead to registration of the vaccine in Brazil. The vaccine would also need to be introduced in the poorest regions of Africa and Asia, where hookworm infection is highly endemic. Ultimately, the vaccine could become an essential tool for achieving hookworm control and elimination, a key target in the 2012 London Declaration on Neglected Tropical Diseases.
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Frequency of sexual dysfunction in women with rheumatic diseases.
Rev Bras Reumatol
PUBLISHED: 04-17-2013
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To assess the prevalence of sexual dysfunction in women followed up at the Rheumatology Outpatient Clinic of the Hospital Universitário de Brasília and of the Hospital das Clínicas da Universidade de São Paulo with the following rheumatic diseases: systemic lupus erythematosus; rheumatoid arthritis; systemic sclerosis; antiphospholipid antibody syndrome; and fibromyalgia.
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Dogs immunized with LBSap vaccine displayed high levels of IL-12 and IL-10 cytokines and CCL4, CCL5 and CXCL8 chemokines in the dermis.
Mol. Immunol.
PUBLISHED: 03-27-2013
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The complex interplay between cytokines and chemokines regulates innate and adaptive immune responses against pathogens; specifically, cytokine and chemokine expression drives activation of immune effector cells and their recruitment to tissue infection sites. Herein, we inoculated dogs with Leishmania braziliensis antigens plus saponin (the LBSap vaccine), as well as with the vaccine components, and then used real-time PCR to evaluate the kinetics of dermal expression of mRNAs of cytokines (IL-12, IFN-?, TNF-?, IL-4, IL-13, TGF-? and IL-10) and chemokines (CCL2, CCL4, CCL5, CCL21 and CXCL8) 1, 12, 24 and 48 h after inoculation. We also evaluated the correlation between cytokine and chemokine expression and dermal cellularity. The LBSap vaccine induced high levels of IL-12 and IL-10 expression at 12 and 24 h, respectively. Furthermore, we observed positive correlations between IL-12 and IL-13 expression, IFN-? and IL-13 expression, and IL-13 and TGF-? expression, suggesting that a mixed cytokine microenvironment developed after immunization with the vaccine. Inoculation with the saponin adjuvant alone induced a chemokine and cytokine expression profile similar to that observed in the LBSap group. CCL4 and CXCL8 chemokine expression was up regulated by the LBSap vaccine. CCL5 expression was initially highest in the LBSap group, but at 48 h, expression was highest in the LB group. Information about the kinetics of the immune response to this vaccine gained using this dog model will help to elucidate the mechanisms of and factors involved in a protective response against Leishmania infection and will aid in establishing rational approaches for the development of vaccines against canine visceral leishmaniasis.
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Cytokine and nitric oxide patterns in dogs immunized with LBSap vaccine, before and after experimental challenge with Leishmania chagasi plus saliva of Lutzomyia longipalpis.
Vet. Parasitol.
PUBLISHED: 02-20-2013
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In the studies presented here, dogs were vaccinated against Leishmania (Leishmania) chagasi challenge infection using a preparation of Leishmania braziliensis promastigote proteins and saponin as adjuvant (LBSap). Vaccination with LBSap induced a prominent type 1 immune response that was characterized by increased levels of interleukin (IL-) 12 and interferon gamma (IFN-?) production by peripheral blood mononuclear cells (PBMC) upon stimulation with soluble vaccine antigen. Importantly, results showed that this type of responsiveness was sustained after challenge infection; at day 90 and 885 after L. chagasi challenge infection, PBMCs from LBSap vaccinated dogs produced more IL-12, IFN-? and concomitant nitric oxide (NO) when stimulated with Leishmania antigens as compared to PBMCs from respective control groups (saponin, LB- treated, or non-treated control dogs). Moreover, transforming growth factor (TGF)-? decreased in the supernatant of SLcA-stimulated PBMCs in the LBSap group at 90 days. Bone marrow parasitological analysis revealed decreased frequency of parasitism in the presence of vaccine antigen. It is concluded that vaccination of dogs with LBSap vaccine induced a long-lasting type 1 immune response against L. chagasi challenge infection.
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Cytokine Pattern of T Lymphocytes in Acute Schistosomiasis mansoni Patients following Treated Praziquantel Therapy.
J Parasitol Res
PUBLISHED: 01-20-2013
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Acute schistosomiasis is associated with a primary exposure and is more commonly seen in nonimmune individuals traveling through endemic regions. In this study, we have focused on the cytokine profile of T lymphocytes evaluated in circulating leukocytes of acute Schistosomiasis mansoni-infected patients (ACT group) before and after praziquantel treatment (ACT-TR group). Our data demonstrated increased values of total leukocytes, eosinophils, and monocytes in both groups. Interestingly, we have observed that patients treated with praziquantel showed increased values of lymphocytes as compared with noninfected group (NI) or ACT groups. Furthermore, a decrease of neutrophils in ACT-TR was observed when compared to ACT group. Analyses of short-term in vitro whole blood stimulation demonstrated that, regardless of the presence of soluble Schistosoma mansoni eggs antigen (SEA), increased synthesis of IFN-? and IL-4 by T-cells was observed in the ACT group. Analyses of cytokine profile in CD8 T cells demonstrated higher percentage of IFN-? and IL-4 cells in both ACT and ACT-TR groups apart from increased percentage of IL-10 cells only in the ACT group. This study is the first one to point out the relevance of CD8 T lymphocytes in the immune response induced during the acute phase of schistosomiasis.
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Induction of immunogenicity by live attenuated Leishmania donovani centrin deleted parasites in dogs.
Vaccine
PUBLISHED: 01-17-2013
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Zoonotic visceral leishmaniasis, caused by the intracellular protozoan parasite Leishmania infantum, is a neglected tropical disease that is often fatal when untreated. Dogs are considered the main reservoir of L. infantum in zoonotic VL as the presence of infected dogs may increase the risk for human infection. Canine visceral leishmaniasis (CVL) is a major veterinary and public health problem in Southern Europe, Middle East and South America. Control of animal reservoirs relies on elimination of seropositive dogs in endemic areas. However, treatment of infected dogs is not considered a favorable approach as this can lead to emergence of drug resistance since the same drugs are used to treat human infections. Therefore, vaccination against CVL remains the best alternative in control of the animal reservoirs. In this study, we present data on the immunogenicity profile of a live attenuated parasite LdCen(-/-) in a canine infection model and compared it to that of Leishmune(®), a commercially available recombinant vaccine. The immunogenicity of the LdCen(-/-) parasites was evaluated by antibody secretion, production of intracytoplasmic and secreted cytokines, activation and proliferation of T cells. Vaccination with LdCen(-/-) resulted in high immunogenicity as revealed by the higher IgGTotal, IgG1, and IgG2 production and higher lymphoproliferative response. Further, LdCen(-/-) vaccinated dogs showed higher frequencies of activated CD4+ and CD8+ T cells, IFN-? production by CD8+ T cells, increased secretion of TNF-? and IL-12/IL-23p40 and decreased secretion of IL-4. These results contribute to the understanding of immunogenicity elicited by live attenuated L. donovani parasites and, consequently, to the development of effective vaccines against visceral leishmaniasis.
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Self-induced fatal air embolism: accidental autoerotic death or suicide?
J. Forensic Sci.
PUBLISHED: 01-12-2013
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Autoeroticism comprises behavior deviations aimed at producing sexual gratification through the manipulation of ones own body. The use of asphyxia and the induction of pain (masochism) are well-known examples. "Atypical forms" of such behaviors have appeared in the literature as isolated cases. Fatal air embolism is most common in women (causing abortion), being very rare in men (urethral trauma). The authors present a probable case of air embolism associated with signs of autoeroticism, instrumented by the delivery of air through a system formed by a compressor (typical of those used in refrigerators), a syringe barrel, a segment of latex tubing (tourniquet), and a needle, which was found inserted into the glans penis of an adult male. The hypothesis of accidental death was chosen due to the findings at the scene. The body was decomposing when found, which hampered the conduction of examinations.
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Intra-operative use of 5-Fluorouracil in pterygium surgery: a comparative study.
Semin Ophthalmol
PUBLISHED: 01-12-2013
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Evaluate the efficacy and safety of intraoperative application of 5-Fluorourail in pterygium surgery and the recurrent pterigyum postoperative.
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LLE experimental data, thermodynamic modeling and sensitivity analysis in the ethyl biodiesel from macauba pulp oil settling step.
Bioresour. Technol.
PUBLISHED: 01-11-2013
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The aim of this study was to obtain experimental data related to liquid–liquid equilibrium (LLE) of systems containing glycerol + ethanol + ethyl biodiesel from macauba pulp oil, perform thermodynamic modeling and simulate the settling step of this biodiesel using simulation software. Binary interaction parameters were adjusted for NRTL and UNIQUAC models. The UNIFAC-LLE and UNIFAC-Dortmund models were used to predict the LLE of the systems. A sensitivity analysis was applied to the settling step to describe the composition of the output streams as a function of ethanol in the feed stream. Ethanol had greater affinity for the glycerol-rich phase. The deviations between experimental data and calculated values were 0.44%, 1.07%, 3.52% and 2.82%, respectively, using the NRTL, UNIQUAC, UNIFAC-LLE and UNIFAC-Dortmund models. Excess ethanol in the feed stream causes losses of ethyl ester in the glycerol-rich stream and high concentration of glycerol in the ester-rich stream.
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Theoretical study of photochemical hydrogen abstraction by triplet aliphatic carbonyls by using density functional theory.
J Phys Chem A
PUBLISHED: 01-07-2013
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The density functional theory (DFT) and quantum theory of atoms in molecules (QTAIM) have been used to study the lowest lying spin states of the photochemical hydrogen abstraction reaction by formaldehyde, acetaldehyde, and acetone in the presence of different hydrogen donors: propane, 2-propanol, and methylamine. Calculations of all the critical points on the PES of these reactions were performed at uB3LYP/6-311++G(d,p). Methylamine is the best hydrogen donor, in thermodynamic and kinetic terms, followed by 2-propanol and finally propane. Secondary C-H hydrogen abstraction in 2-propanol and C-H abstraction in methylamine is thermodynamically and kinetically favored with respect to hydrogen abstraction from the OH and NH functional groups. Charge transfer takes place before the transition state when methylamine is the hydrogen donor, and for other hydrogen donors, charge transfer begins only in the transition state. The extent of the charge transfer in the transition states corresponds to about 50% of the total change in electron density of the oxygen atom of the T(1) carbonyl compounds during the course of the hydrogen abstraction reactions. The effect of solvent was investigated using the continuum solvation model for the reaction of triplet acetaldehyde in acetonitrile, which resulted in a barrierless transition state for hydrogen abstraction from methylamine.
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Cell apoptosis induced by hookworm antigens: a strategy of immunomodulation.
Front Biosci (Elite Ed)
PUBLISHED: 01-02-2013
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While several mechanisms of immunoregulation have been demonstrated for hookworm and other neglected tropical infections, the influence of apoptosis in the immunomodulation of hookworm infection is still poorly understood. In this study, we demonstrate the cytotoxic and pro-apoptotic activity of hookworm antigens in Jurkat T cells, mesenteric lymph nodes lymphocytes of healthy and hookworm-infected hamsters and during human natural infection. Our results showed that in vitrostimulation of Jurkat T cells with antigens induces a significant decrease of cell viability leading to a relevant increase of apoptotic cells. Similar results were also observed in experimental conditions, for both healthy and hookworm-infected hamsters` lymphocytes. Flow cytometric analysis demonstrated that hookworm-infected patients presented a significant increase of CD4+, CD8+, and CD19+lymphocytes in early and/or late apoptosis when compared with non-infected individuals. The downmodulation of TNF receptors, as well as the up-regulation of the pro-apoptotic genes belonging to the BCL-2 and P53 families, suggest that hookworm antigens induced apoptosis by an intrinsic mitochondrial pathway, acting as a sophisticated strategy to safeguard parasite long-term survival in their hosts.
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[Functional feeding groups of macroinvertebrates in Gaira river, Colombia].
Rev. Biol. Trop.
PUBLISHED: 12-30-2011
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Tropical rivers are frequently described on their biodiversity but few studies have considered the ecological value of this richness in their food webs. We determined the trophic structure of aquatic macroinvertebrate communities (expressed in the richness and abundance of taxa and biomass proportions of different functional feeding groups) at the level of the river, stretch and microhabitats (functional units - UFs). We evaluated the spatial and temporal variation of these descriptors during wet and dry events, and selected three sites associated with different altitudinal belts. We reported 109 taxa, with 11167 individuals who contributed 107.11g of biomass. Density of macroinvertebrates was favored with increasing height, and biomass showed the opposite pattern (K-W = 10.1, d.f. = 1, p < 0.05), due to the addition of large crustaceans (Macrobrachium), and the taxa diversity was higher in the middle stretch of the river (H=3.16). The Gaira stream runs through a mid-sized river basin, for this reason we found mainly bedrock (epilithon = 50.5%), gravel and sand (43.7%). The functional unit with more habitat and food resources that contains a higher abundance of leaf litter macroinvertebrates was foliage followed by epilithon, fine sediment and gravel-sand (K-W = 25.3, d.f. = 3, p < 0.05). The biomass values of these organisms were higher in leaves followed by gravel-sands, epilithon and sediment (K-W = 15.3, d.f. = 3, p < 0.05). Autochthonous biomass input by different functional feeding groups can be considered very low, but they define the functionality of the stream, being represented almost exclusively by shredders (Macrobrachium, 73%), present only in the lower reaches, followed by shredder Leptonema with 15%, located mostly in the upper reaches and predatory stoneflies of the genus Anacroneuria to 6.56%, which dominated in the middle stretch of stream. Excluding Macrobrachium from the analysis, there was dominance of Anacroneuria in the lower reaches. Between rainfall and drought events, biomass of functional feeding groups was higher in rain (W = 10.1, d.f. = 1, p < 0.05), favoring the growth of decapods, but the abundance was much higher during drought events.
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Probing the relationships between molecular conformation and intermolecular contacts in N,N-dibenzyl-N-(furan-2-carbonyl)thiourea.
Acta Crystallogr C
PUBLISHED: 10-11-2011
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In the crystal structure of the title compound, C(20)H(18)N(2)O(2)S, molecules are linked by bifurcated C-H···O hydrogen-bond interactions, giving rise to chains whose links are composed of alternating centrosymmetrically disposed pairs of molecules and characterized by R(2)(2)(10) and R(2)(2)(20) hydrogen-bonding motifs. Also, N-H···S hydrogen bonds form infinite zigzag chains along the [010] direction, which exhibit the C(4) motif. Hirshfeld surface and fingerprint plots were used to explore the intermolecular interactions in the crystal structure. This analysis confirms the important role of C-H···O hydrogen bonds in the molecular conformation and in the crystal structure, providing a potentially useful tool for a full understanding of the intermolecular interactions in acylthiourea derivatives.
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Genetic epidemiology of Chagas disease.
Adv. Parasitol.
PUBLISHED: 08-09-2011
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Genetic epidemiological approaches hold great promise for improving the understanding of the determinants of susceptibility to infection with Trypanosoma cruzi and the causes of differential disease outcome in T. cruzi-infected individuals. To date, a variety of approaches have been used to understand the role of genetic factors in Chagas disease. Quantitative genetic techniques have been used to estimate the heritabilities for seropositivity for T. cruzi infection and traits that are associated with disease progression in chronic T. cruzi infection. These studies have demonstrated that a significant proportion of the variation in seropositivity and a number of traits related to Chagas disease progression is attributable to genetic factors. Candidate gene studies have provided intriguing evidence for the roles of numerous individual genes in determining cardiac outcomes in chronically infected individuals. Recent results from a long-term study of Chagas disease in a rural area of Brazil have documented that over 60% of the variation in seropositivity status is attributable to genetic factors in that population. Additionally, there are significant genetic effects on a number of electrocardiographic measures and other Chagas disease-related traits. The application of genome-wide approaches will yield new evidence for the roles of specific genes in Chagas disease.
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Immune modulation in primary vaccinia virus zoonotic human infections.
Clin. Dev. Immunol.
PUBLISHED: 07-12-2011
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In 2010, the WHO celebrated the 30th anniversary of the smallpox eradication. Ironically, infections caused by viruses related to smallpox are being increasingly reported worldwide, including Monkeypox, Cowpox, and Vaccinia virus (VACV). Little is known about the human immunological responses elicited during acute infections caused by orthopoxviruses. We have followed VACV zoonotic outbreaks taking place in Brazil and analyzed cellular immune responses in patients acutely infected by VACV. Results indicated that these patients show a biased immune modulation when compared to noninfected controls. Amounts of B cells are low and less activated in infected patients. Although present, T CD4(+) cells are also less activated when compared to noninfected individuals, and so are monocytes/macrophages. Similar results were obtained when Balb/C mice were experimentally infected with a VACV sample isolated during the zoonotic outbreaks. Taking together, the data suggest that zoonotic VACVs modulate specific immune cell compartments during an acute infection in humans.
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Necator americanus and helminth co-infections: further down-modulation of hookworm-specific type 1 immune responses.
PLoS Negl Trop Dis
PUBLISHED: 07-08-2011
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Helminth co-infection in humans is common in tropical regions of the world where transmission of soil-transmitted helminths such as Ascaris lumbricoides, Trichuris trichiura, and the hookworms Necator americanus and Ancylostoma duodenale as well as other helminths such as Schistosoma mansoni often occur simultaneously.
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Weak C-H···Cl-Pd interactions toward conformational polymorphism in trans-dichloridobis(triphenylphosphane)palladium(II).
Acta Crystallogr C
PUBLISHED: 06-16-2011
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A new triclinic polymorph of the title compound, [PdCl(2)(C(18)H(15)P)(2)], has two independent molecules in the unit cell, with the Pd atoms located on inversion centres. One molecule has an eclipsed conformation, whereas the second molecule adopts a gauche conformation. The molecules with a gauche conformation are involved in weak intermolecular C-H···Cl-Pd interactions with symmetry-related molecules. It is suggested that C-H···Cl-Pd interactions are mainly responsible for the existence of conformational differences, which contribute to the polymorph formation. In the crystal, there are layers of eclipsed and gauche molecules separated by normal van der Waals interactions.
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A regulatory instead of an IL-17 T response predominates in Helicobacter pylori-associated gastritis in children.
Microbes Infect.
PUBLISHED: 06-14-2011
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Th17 cells seem to have an important role in the efficacy of vaccines against Helicobacter pylori. Because children are a target group for human vaccination and Th17/T(reg) cells have intrinsically linked and antagonic commitments, we compared the gastric levels of Th17- and T(reg)-associated cytokines of children and adults. IL-6, IL-10 and TGF-?1 levels and Foxp3(+) cell numbers were higher, but IL-1?, IL-17A and IL-23 were lower in infected children than in infected adults. In conclusion T(reg) instead of Th17 cell response to H. pylori-infection predominates in children.
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Regulatory T cells phenotype in different clinical forms of Chagas disease.
PLoS Negl Trop Dis
PUBLISHED: 05-31-2011
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CD25(High) CD4+ regulatory T cells (Treg cells) have been described as key players in immune regulation, preventing infection-induced immune pathology and limiting collateral tissue damage caused by vigorous anti-parasite immune response. In this review, we summarize data obtained by the investigation of Treg cells in different clinical forms of Chagas disease. Ex vivo immunophenotyping of whole blood, as well as after stimulation with Trypanosoma cruzi antigens, demonstrated that individuals in the indeterminate (IND) clinical form of the disease have a higher frequency of Treg cells, suggesting that an expansion of those cells could be beneficial, possibly by limiting strong cytotoxic activity and tissue damage. Additional analysis demonstrated an activated status of Treg cells based on low expression of CD62L and high expression of CD40L, CD69, and CD54 by cells from all chagasic patients after T. cruzi antigenic stimulation. Moreover, there was an increase in the frequency of the population of Foxp3+ CD25(High)CD4+ cells that was also IL-10+ in the IND group, whereas in the cardiac (CARD) group, there was an increase in the percentage of Foxp3+ CD25(High) CD4+ cells that expressed CTLA-4. These data suggest that IL-10 produced by Treg cells is effective in controlling disease development in IND patients. However, in CARD patients, the same regulatory mechanism, mediated by IL-10 and CTLA-4 expression is unlikely to be sufficient to control the progression of the disease. These data suggest that Treg cells may play an important role in controlling the immune response in Chagas disease and the balance between regulatory and effector T cells may be important for the progression and development of the disease. Additional detailed analysis of the mechanisms on how these cells are activated and exert their function will certainly give insights for the rational design of procedure to achieve the appropriate balance between protection and pathology during parasite infections.
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Influence of clinical status and parasite load on erythropoiesis and leucopoiesis in dogs naturally infected with leishmania (Leishmania) chagasi.
PLoS ONE
PUBLISHED: 03-20-2011
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The bone marrow is considered to be an important storage of parasites in Leishmania-infected dogs, although little is known about cellular genesis in this organ during canine visceral leishmaniasis (CVL).
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Excretory-secretory products from hookworm l(3) and adult worms suppress proinflammatory cytokines in infected individuals.
J Parasitol Res
PUBLISHED: 03-18-2011
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We compared the effects of larval and adult worm excretory-secretory (ES) products from hookworm on the proliferative responses and cytokine secretion in peripheral blood mononuclear cells (PBMCs) from hookwormpatients and egg-negative, nonendemic controls. When compared with negative controls, mitogen-stimulated PBMC from hookworm-infected individuals showed a significantly reduced proliferative response when adult worm ES antigen was added to the cultures. Furthermore, in hookworm-infected individuals a significant downmodulation of inflammatory interleukin (IL)-6 and tumor necrosis factor (TNF)-? secretion resulted when PBMCs were stimulated with mitogen in combination with larval or adult worm ES. Both, interferon (IFN)-? and IL-10 secretion were significantly lower in stimulated PBMC from infected individuals; however the IFN-?/IL-10 ratio was much lower in hookworm-infected patients. Comparable effects, although at lower concentrations, were achieved when PBMCs from both groups were incubated with living hookworm third-stage larvae. We suggest that hookworm ES products downmodulate proliferative responses and inflammation during the chronic phase of the disease and facilitate early larval survival or adult worm persistence in the gut.
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Tetrachlorocarbonyliridates: water-soluble carbon monoxide releasing molecules rate-modulated by the sixth ligand.
Inorg Chem
PUBLISHED: 02-15-2011
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A new family of compounds is presented as potential carbon monoxide releasing molecules (CORMs). These compounds, based on tetrachlorocarbonyliridate(III) derivatives, were synthesized and fully characterized by X-ray diffraction, electrospray mass spectrometry, IR, NMR, and density functional theory calculations. The rate of CO release was studied via the myoglobin assay. The results showed that the rate depends on the nature of the sixth ligand, trans to CO, and that a significant modulation on the release rate can be produced by changing the ligand. The reported compounds are soluble in aqueous media, and the rates of CO release are comparable with those for known CORMs, releasing CO at a rate of 0.03-0.58 ?M min(-1) in a 10 ?M solution of myoglobin and 10 ?M of the complexes.
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N-Benzoyl-N,N-dimethyl-thio-urea.
Acta Crystallogr Sect E Struct Rep Online
PUBLISHED: 02-10-2011
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In the title compound, C(10)H(12)N(2)OS, the amide NCO group is twisted relative to the thio-ureido SCN(2) group, forming a dihedral angle of 55.3?(2)°. The crystal packing shows inter-molecular N-H?S and weak C-H?O inter-actions, the former giving rise to the formation of centrosymmetric R(2) (2)(8) dimers.
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Induction of CD4(+)CD25(+)FOXP3(+) regulatory T cells during human hookworm infection modulates antigen-mediated lymphocyte proliferation.
PLoS Negl Trop Dis
PUBLISHED: 01-10-2011
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Hookworm infection is considered one of the most important poverty-promoting neglected tropical diseases, infecting 576 to 740 million people worldwide, especially in the tropics and subtropics. These blood-feeding nematodes have a remarkable ability to downmodulate the host immune response, protecting themselves from elimination and minimizing severe host pathology. While several mechanisms may be involved in the immunomodulation by parasitic infection, experimental evidences have pointed toward the possible involvement of regulatory T cells (Tregs) in downregulating effector T-cell responses upon chronic infection. However, the role of Tregs cells in human hookworm infection is still poorly understood and has not been addressed yet. In the current study we observed an augmentation of circulating CD4(+)CD25(+)FOXP3(+) regulatory T cells in hookworm-infected individuals compared with healthy non-infected donors. We have also demonstrated that infected individuals present higher levels of circulating Treg cells expressing CTLA-4, GITR, IL-10, TGF-? and IL-17. Moreover, we showed that hookworm crude antigen stimulation reduces the number of CD4(+)CD25(+)FOXP3(+) T regulatory cells co-expressing IL-17 in infected individuals. Finally, PBMCs from infected individuals pulsed with excreted/secreted products or hookworm crude antigens presented an impaired cellular proliferation, which was partially augmented by the depletion of Treg cells. Our results suggest that Treg cells may play an important role in hookworm-induced immunosuppression, contributing to the longevity of hookworm survival in infected people.
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Enteroglial cells act as antigen-presenting cells in chagasic megacolon.
Hum. Pathol.
PUBLISHED: 01-03-2011
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Chagas disease is one of the most serious parasitic diseases of Latin America, with a social and economic impact far outweighing the combined effects of other parasitic diseases such as malaria, leishmaniasis, and schistosomiasis. In the chronic phase of this disease, the destruction of enteric nervous system components leads to megacolon development. Besides neurons, the enteric nervous system is constituted by enteric glial cells, representing an extensive but relatively poorly described population within the gastrointestinal tract. Several lines of evidence suggest that enteric glial cells represent an equivalent of central nervous system astrocytes. Previous data suggest that enteric glia and neurons are active in the enteric nervous system during intestinal inflammatory and immune responses. To evaluate whether these cells act as antigen-presenting cells, we investigated the expression of molecules responsible for activation of T cells, such as HLA-DR complex class II and costimulatory molecules (CD80 and CD86), by neurons and enteric glial cells. Our results indicate that only enteric glial cells of chagasic patients with megacolon express HLA-DR complex class II and costimulatory molecules, and hence they present the attributes necessary to act as antigen-presenting cells.
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Evidence of long term benefit of morbidity reduction due to praziquantel treatment against schistosoma mansoni in kigungu fishing village in entebbe, Uganda.
Afr J Infect Dis
PUBLISHED: 01-01-2011
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Praziquantel (PZQ) is efficacious against Schistosoma mansoni. This was prospective cohort study. This study was carried out at Kigungu fishing village, Entebbe, Uganda. The goal of the study was to establish cost effective regiment for mass drug administration (MDA) of Praziquentel in the morbidity reduction of S.mansoni infection. In January 2004, nine hundred and forty five (945) participants were registered in this study. Our analysis was based on examining microscopically three slides prepared from each of 945 stool specimens delivered by each of the participant using modified Kato/Katz method. These included male and female, children and adults living in Kigungu fishing village in Entebbe Uganda. In total 901, cohorts were re-examined for infections clearance six months later in July 2004 and 18 months later in June 2005, 625 cohorts were again re-evaluated for S.mansoni infections after the baseline study. At baseline, (448) of 945 (47.5%) cohorts were S. mansoni positive. All these participants were treatment with a single oral dose of praziquantel at 40mg/kg. At the same time, 495 (52.5%) were S. mansoni negative. Of the 625 (66.3%) cohorts who came back for final review, 80 (12.8%) were still positive for S. mansoni while 210 (33.6%) remained negative after the base line treatment with praziquantel. On the other hand 103 (16.3%) of cohorts who were initially negative at the base line became S.mansoni positive after 18 months and 213(34.1%) remained negative for S.mansoni. The force of re-infection after six months was significant {(P=0.0001), (OR 0.47) CI at 95% (0.31-0.71)}. Nevertheless the force of reinfection was not significant after 18 months {(P=0.766), (OR 0.95) CI at 95% (0.68-1.34)}.The geometric mean eggs excretion of the 80 cohorts who were S.mansoni positive at 18 months was 151.967.This did not reach the geometric mean egg excreted by the same cohorts at baseline which was 285.05. The egg excretion was reduced by 46.8%. Similarly there was marked decrease in clinical symptoms amongst the cohorts. Our study suggests evidence of long-term benefit of praziquantel in Kigungu and that a yearly administration of praziquantel to the community could be a regiment for mass drug administration (MAD) for this community to control schistosomiasis morbidity.
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Association of mast cell, eosinophil leucocyte and microvessel densities in actinic cheilitis and lip squamous cell carcinoma.
Histopathology
PUBLISHED: 12-21-2010
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To determine the contributions of mast cells (MC), eosinophil leucocytes (EL) and microvessel density (MVD) in lip carcinogenesis, and to establish the relationships between these biomarkers and their possible prognostic value in lip squamous cell carcinoma (LSCC).
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Cytokine and transcription factor profiles in the skin of dogs naturally infected by Leishmania (Leishmania) chagasi presenting distinct cutaneous parasite density and clinical status.
Vet. Parasitol.
PUBLISHED: 11-07-2010
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The immune response in the skin of dogs infected with Leishmania chagasi and its association with distinct levels of tissue parasitism and clinical progression of canine visceral leishmaniasis (CVL) are poorly understood and limited studies are available. A detailed analysis of the profiles of cytokines (IFN-?, IL-4, IL-5, IL-10, IL-12, IL-13, TGF-?1 and TNF-?) and transcription factors (T-bet, GATA-3 and FOXP3) in the skin of 35 naturally infected dogs was carried out using real-time PCR alongside determinations of skin parasite density and the clinical status of CVL. A mixed cytokine profile with high levels of expression of IFN-?, TNF-? and IL-13 was determined in asymptomatic dogs. Additionally, the levels of transcription factors GATA-3 and FOXP3 were correlated with the asymptomatic disease. A mixed cytokine profile was also observed during active CVL. Moreover, high levels of IL-10 and TGF-?1, concomitant with the low expression of IL-12, may represent a key condition that allows persistence of parasite replication in the skin. The results obtained indicate that in asymptomatic disease or lower levels of skin parasite density, a mixed inflammatory, regulatory immune response profile may be of major relevance for both the maintenance of the clinical status of the dogs as well as for parasite persistence and replication at low levels.
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Qualitative and quantitative immunohistochemical evaluation of iNOS expression in the spleen of dogs naturally infected with Leishmania chagasi.
Parasitol. Res.
PUBLISHED: 10-04-2010
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Nitric oxide (NO), the product of the nitric oxide synthase enzymes has been detected in Leishmania-infected animals. Besides its role on the immunity to infection, the role of NO and the inducible nitric oxide synthase (iNOS) in the pathogenesis of canine visceral leishmaniasis (CVL) is not well understood. This study aimed at evaluating immunohistochemically the iNOS expression in the spleen of dogs naturally infected (ID) with Leishmania (L.) chagasi compared with non-infected dogs (NID). The ID was grouped according to the clinical form and the parasite load. Symptomatic dogs (SD) presented higher parasite load in relation to oligosymptomatic (OD) and asymptomatic (AD). The qualitative expression of iNOS was observed only in ID. SD presented strong and prominent labeling of iNOS, followed by OD and AD. Quantitatively, the results showed that the median expression of iNOS was higher in SD and OD compared to NID. Also, dog spleens with high parasitism load showed marked iNOS expression. Taken together, the results suggest that the expression of iNOS in the spleen of infected dogs with CVL was associated with clinical worsening of the disease and with high parasitism.
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The role of population movement in the epidemiology and control of schistosomiasis in Brazil: a preliminary typology of population movement.
Mem. Inst. Oswaldo Cruz
PUBLISHED: 08-20-2010
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This paper examines recent developments in migration studies. It reviews literature related to the potential role of internal population movement in the occurrence of schistosomiasis in Brazil and modifies Protheros typology of population movement for use in Brazil. This modified classification system may contribute to a better understanding of schistosome transmission as well as improved research and control programs. The results of this study indicate that population movement in Brazil primarily involves economically-motivated rural-urban and interregional movement. However, several movement patterns have become increasingly important in recent years as a result of changing socioeconomic and urbanisation dynamics. These patterns include urban-urban, intracity and urban-rural movement as well as the movement of environmental refugees and tourists. Little is known about the epidemiological significance of these patterns. This paper also highlights the role of social networks in the decision to migrate and to settle. Protheros classic population movement typology categorises movement as either one-way migrations or circulations and examines them along spatial and temporal scales. However, the typology must be modified as epidemiological information about new patterns becomes available. This paper identifies areas that require further research and offers recommendations that can improve the measurement and spatial analysis of the relationship between population movement and schistosomiasis.
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Rural tourism: a risk factor for schistosomiasis transmission in Brazil.
Mem. Inst. Oswaldo Cruz
PUBLISHED: 08-20-2010
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This paper reports an outbreak of acute schistosomiasis among 38 tourists who rented a country house in the district of Igarapé, the metropolitan region of Belo Horizonte, Brazil, during a holiday period in 2006. A total number of 32 individuals were positive for Schistosoma mansoni. Results of stool examinations revealed individual S. mansoni egg counts per gram of faeces (epg) ranging from 4-768 epg with a geometric mean egg count of 45. The most frequent clinical symptoms were abdominal pain (78.1%), headache (75%), fever (65.6%), dry cough (65.2%) and both diarrhoea and asthenia (59.4%). A malacological survey of the area, where 22 specimens of Biomphalaria glabrata were collected, revealed three (13.6%) specimens eliminating Schistosoma cercariae. This investigation re-confirms a recently described pattern of schistosomiasis infection, resulting in the acute form of the disease and connected to rural tourism, which contributes to the spread of the disease among the middle-class and into non-endemic areas. The lack of specific knowledge about acute schistosomiasis among health services causes an increased number of unnecessary diagnostic procedures and delays in accurate diagnosis and treatment, resulting in considerable discomfort for the patients.
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Seric chemokines and chemokine receptors in eosinophils during acute human schistosomiasis mansoni.
Mem. Inst. Oswaldo Cruz
PUBLISHED: 08-20-2010
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The recruitment of circulating eosinophils by chemokines and chemokine receptors plays an important role in the inflammation process in acute human schistosomiasis. Our main focus has been on the plasma chemokines (CXCL8/CCL2/CCL3/CCL24) and chemokine receptors (CCR2/CCR3/CCR5/CXCR1/CXCR2/CXCR3/CXCR4) expressed by circulating eosinophils from acute Schistosoma mansoni infected patients (ACT). Our studies compared ACT patients and healthy individuals as a control group. Our major findings demonstrated a plethora of chemokine secretion with significantly increased secretion of all chemokines analysed in the ACT group. Although no differences were detected for beta-chemokine receptors (CCR2, CCR3 and CCR5) or alpha-chemokine receptors (CXCR3 and CXCR4), a significantly lower frequency of CXCR1+ and CXCR2+ eosinophils in the ACT group was observed. The association between chemokines and their chemokine receptors revealed that acutely infected schistosome patients displaying decreased plasma levels of CCL24 are the same patients who presented enhanced secretion of CCL3, as well as increased expression of both the CCR5 and CXCR3 chemokine receptors. These findings suggest that CCL24 may influence the kinetics of chemokines and their receptors and eosinophils recruitment during human acute schistosomiasis mansoni.
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Genetic and household determinants of predisposition to human hookworm infection in a Brazilian community.
J. Infect. Dis.
PUBLISHED: 08-05-2010
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Predisposition to heavy or light human hookworm infection is consistently reported in treatment-reinfection studies. A significant role for host genetics in determining hookworm infection intensity has also been shown, but the relationship between host genetics and predisposition has not been investigated.
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A laser flash photolysis and theoretical study of hydrogen abstraction from phenols by triplet alpha-naphthoflavone.
Phys Chem Chem Phys
PUBLISHED: 07-08-2010
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The hydrogen abstraction (HA) reaction by the triplet of alpha-naphthoflavone (1) has been investigated experimentally by the use of laser flash photolysis (LFP) and theoretically with density functional theory (DFT) and atoms in molecules (AIM). The triplet excited state of 1, in acetonitrile, has an absorption maximum at 430 nm and lifetime of 10 micros. The quenching rate constants for the triplet of 1 with 1,4-cyclohexadiene, substituted phenols and amines were determined. The low reactivity of this ketone with respect to HA from 1,4-cyclohexadiene is in accord with a pi,pi* excited state. HA from phenols in acetonitrile is proposed to occur in a diffusion controlled reaction from free phenol based upon the determination of the Abraham beta(H)(2) value for acetonitrile and correction of the quenching rate constants for hydrogen bonding of the phenols to acetonitrile. A molecular orbital analysis of the triplet (SOMO and SOMO-1) of 1 reveals contributions from the carbonyl oxygen atom, but principally from the alpha-carbon and the associated pi-bond network, consistent with a pi,pi* excited state. From a thermodynamic point of view, the triplet HA from phenol to oxygen of the carbonyl group is 17 kcal mol(-1) less demanding than the transfer to the alpha-carbon, consistent with the acidic nature of the phenolic hydrogen atom. DFT and AIM analysis of the hydrogen abstraction reaction reveals that the transition state (TS) is pseudo-symmetrically polarized and that HA in the hydrogen bonded exciplex occurs in a concerted manner but not necessarily by simultaneous electron and proton transfer.
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Clinical signs, diagnosis, and case reports of Vaccinia virus infections.
Braz J Infect Dis
PUBLISHED: 06-22-2010
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Vaccinia virus is responsible for a zoonosis that usually affects cattle and human beings in Brazil. The initial clinical signs of the infection are focal red skin areas, fever, and general symptoms similar to those of a cold. Then, pustules and ulcerated lesions surrounded by edema and erythema follow, as well as local lymphadenopathy that can last for weeks. Cure and healing of the lesions occur over several weeks, leaving a typical scar in the skin of people and animals affected. The infection definitive diagnosis is made through morphological characterization of the virus by use of electron microscopy, followed by PCR for specific viral genes. Since 1963, circulating orthopoxviruses in infectious outbreaks in several regions of Brazil have been reported. Later, the etiological agent of those infections was characterized as samples of Vaccinia virus. In addition, the widespread use of those viruses in research laboratories and mass vaccination of militaries have contributed to increase the cases of those infections worldwide. Thus, several epidemiological and clinical studies are required, as well as studies of viral immunology, public health, and economic impact, because little is known about those Vaccinia virus outbreaks in Brazil.
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Health education through analogies: preparation of a community for clinical trials of a vaccine against hookworm in an endemic area of Brazil.
PLoS Negl Trop Dis
PUBLISHED: 06-02-2010
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Obtaining informed consent for clinical trials is especially challenging when working in rural, resource-limited areas, where there are often high levels of illiteracy and lack of experience with clinical research. Such an area, a remote field site in the northeastern part of the state of Minas Gerais, Brazil, is currently being prepared for clinical trials of experimental hookworm vaccines. This study was conducted to assess whether special educational tools can be developed to increase the knowledge and comprehension of potential clinical trial participants and thereby enable them to make truly informed decisions to participate in such research.
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Plasmodium vivax: induction of CD4+CD25+FoxP3+ regulatory T cells during infection are directly associated with level of circulating parasites.
PLoS ONE
PUBLISHED: 02-19-2010
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Circulation CD4(+)CD25(+)FoxP3(+) regulatory T cells (Tregs) have been associated with the delicate balancing between control of overwhelming acute malaria infection and prevention of immune pathology due to disproportionate inflammatory responses to erythrocytic stage of the parasite. While the role of Tregs has been well-documented in murine models and P. falciparum infection, the phenotype and function of Tregs in P. vivax infection is still poorly characterized. In the current study, we demonstrated that patients with acute P. vivax infection presented a significant augmentation of circulating Tregs producing anti-inflammatory (IL-10 and TGF-beta) as well as pro-inflammatory (IFN-gamma, IL-17) cytokines, which was further positively correlated with parasite burden. Surface expression of GITR molecule and intracellular expression of CTLA-4 were significantly upregulated in Tregs from infected donors, presenting also a positive association between either absolute numbers of CD4(+)CD25(+)FoxP3(+)GITR(+) or CD4(+)CD25(+)FoxP3(+)CTLA-4(+) and parasite load. Finally, we demonstrate a suppressive effect of Treg cells in specific T cell proliferative responses of P. vivax infected subjects after antigen stimulation with Pv-AMA-1. Our findings indicate that malaria vivax infection lead to an increased number of activated Treg cells that are highly associated with parasite load, which probably exert an important contribution to the modulation of immune responses during P. vivax infection.
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Schistosoma mansoni Stomatin like protein-2 is located in the tegument and induces partial protection against challenge infection.
PLoS Negl Trop Dis
PUBLISHED: 02-09-2010
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Schistosomiasis affects more than 200 million individuals worldwide, with a further 650 million living at risk of infection, constituting a severe health problem in developing countries. Even though an effective treatment exists, it does not prevent re-infection, and the development of an effective vaccine still remains the most desirable means of control for this disease.
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Systemic and compartmentalized immune response in canine visceral leishmaniasis.
Vet. Immunol. Immunopathol.
PUBLISHED: 08-15-2009
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Human visceral leishmaniasis (VL) and canine visceral leishmaniasis (CVL) are the most important emerging diseases with high prevalence in Latin American countries and are mainly caused by Leishmania (L.) chagasi (Syn=L. infantum). CVL has a great impact on Brazilian public health because domestic dogs are the most important VL peri-domicile reservoirs in both urban and peri-urban areas. Our findings highlight the complexity of cellular immunological events related to the natural infection from dogs by L. chagasi, additionally correlating major peripheral blood phenotypic markers with clinical status and tissues parasite density. Our main results demonstrated that lower frequency of circulating B cells and monocytes are important markers of severe CVL, whereas increased levels of CD8+ lymphocytes appear to be the major phenotypic feature of asymptomatic disease. Determination of the isotypes patterns during CVL demonstrated that asymptomatic dogs and those with low parasitism are associated with an increase of IgG1, while the symptomatic dogs and those with high parasitism are associated with an increase of IgG, IgG2, IgM, IgA and IgE immunoglobulins. Pioneer findings obtained by our group showed a correlation between clinical status of CVL with degree of tissue parasite density. This data demonstrated that asymptomatic dogs presented low parasitism while symptomatic dogs are associated with high parasite load in various tissues such as skin, bone marrow and spleen. We have also investigated the association between tissue parasitism and CVL clinical forms. Regardless of clinical status, skin and spleen are the major sites of high parasite density during ongoing CVL. Furthermore, we demonstrated that bone marrow and spleen parasite density are the most reliable parasitological markers to decode the clinical status of CVL. In this article, we have reviewed some aspects of the histopathological and immunological events occurring in natural and experimental L. chagasi/L. infantum infection, pointing out the main L. chagasi-parasitized tissue. We have discussed the importance of the association between parasite density, immunological/histopathological aspects and clinical status of the CVL, their current applications, challenges for the future and potential opportunities in CVL research.
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Candidate gene analysis of ocular toxoplasmosis in Brazil: evidence for a role for toll-like receptor 9 (TLR9).
Mem. Inst. Oswaldo Cruz
PUBLISHED: 08-06-2009
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Toxoplasma gondii infection is an important mediator of ocular disease in Brazil more frequently than reported from elsewhere. Infection and pathology are characterized by a strong proinflammatory response which in mice is triggered by interaction of the parasite with the toll-like receptor (TLR)/MyD88 pathway. A powerful way to identify the role of TLRs in humans is to determine whether polymorphisms at these loci influence susceptibility to T. gondii-mediated pathologies. Here we report on a small family-based study (60 families; 68 affected offspring) undertaken in Brazil which was powered for large effect sizes using single nucleotide polymorphisms with minor alleles frequencies > 0.3. Of markers in TLR2, TLR5 and TLR9 that met these criteria, we found an association Family Based Association Tests [(FBAT) Z score = 4.232; p = 1.5 x 10-5; p corrected = 1.2 x 10-4] between the C allele (frequency = 0.424; odds ratio = 7; 95% confidence interval 1.6-30.8) of rs352140 at TLR9 and toxoplasmic retinochoroiditis in Brazil. This supports the hypothesis that direct interaction between T. gondii and TLR9 may trigger proinflammatory responses that lead to severe pathologies such as the ocular disease that is associated with this infection in Brazil.
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A phase-stabilized carbon nanotube fiber laser frequency comb.
Opt Express
PUBLISHED: 08-06-2009
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A frequency comb generated by a 167 MHz repetition frequency erbium-doped fiber ring laser using a carbon nanotube saturable absorber is phase-stabilized for the first time. Measurements of the in-loop phase noise show an integrated phase error on the carrier envelope offset frequency of 0.35 radians. The carbon nanotube fiber laser comb is compared with a CW laser near 1533 nm stabilized to the nu(1) + nu(3) overtone transition in an acetylene-filled kagome photonic crystal fiber reference, while the CW laser is simultaneously compared to another frequency comb based on a Cr:Forsterite laser. These measurements demonstrate that the stability of a GPS-disciplined Rb clock is transferred to the comb, resulting in an upper limit on the locked combs frequency instability of 1.2 x 10(-11) in 1 s, and a relative instability of <3 x 10(-12) in 1 s. The carbon nanotube laser frequency comb offers much promise as a robust and inexpensive all-fiber frequency comb with potential for scaling to higher repetition frequencies.
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Schistosoma mansoni infection in a rural area of the Jequitinhonha Valley, Minas Gerais, Brazil: analysis of exposure risk.
Acta Trop.
PUBLISHED: 08-05-2009
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This study examines the relative contribution of age-specific total IgE levels, eosinophils and water contact behavior to the prevalence and intensity (geometric mean egg counts) of Schistosoma mansoni infection in the poor rural population of Virgem das Graças in northern Minas Gerais State. In bivariate analysis, age was strongly correlated with both prevalence and intensity of infection, while eosinophil levels with prevalence only (p<0.0001); IgE levels and 5 demographic and socioeconomic variables were moderately correlated with prevalence (p<0.05), as were number of persons per room and TBM (total body minutes) with egg counts. In multivariate analysis, after controlling for demographic and socioeconomic factors, only total IgE levels were significantly correlated with both prevalence (p=0.248, 95% CI=1.01-1.11) and intensity (p=0.0217, 95% CI=0.01-0.14) of infection and eosinophil levels with prevalence (p=0.0005, 95% CI=1.07-1.24). Although any causal relationship cannot be confirmed by a cross-sectional study, we demonstrated an associated decrease in prevalence and intensity of S. mansoni infection with increased IgE levels.
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The Wnt signaling pathway and rheumatoid arthritis.
Autoimmun Rev
PUBLISHED: 07-16-2009
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The Wnt signaling pathways play a key role in cell renewal, and there are two such pathways. In patients with rheumatoid arthritis (RA), the synovial membrane expresses genes such as Wnt and Fz at higher levels than those observed in patients without RA. The Wnt proteins are glycoproteins that bind to receptors of the Fz family on the cell surface. The Wnt/Fz complex controls tissue formation during embryogenesis, as well as throughout the process of limb development and joint formation. Recent studies have suggested that this signaling pathway plays a role in the pathophysiology of RA. Greater knowledge of the role of the Wnt signaling pathway in RA could improve understanding of the differences in RA clinical presentation and prognosis. Further studies should also focus on Wnt family members as molecular targets in the treatment of RA.
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Alterations in phenotypic profiles of peripheral blood cells from patients with human American cutaneous leishmaniasis following treatment with an antimonial drug and a vaccine.
Acta Trop.
PUBLISHED: 07-08-2009
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The susceptibility or resistance of a vertebrate host to leishmaniasis is related to the species of Leishmania and to the host immune response of the host. In the present study, the phenotypic profiles of the peripheral blood cells of patients with American cutaneous leishmaniasis (ACL) were evaluated before and after receiving three different therapeutic regimens. The study population comprised 24 patients, living in an ACL-endemic area of Caratinga (MG, Brazil), who had been diagnosed as ACL-positive on the basis of characteristic lesions, the Montenegro skin reactivity test, and/or positive parasitology. Subjects were divided into three groups and received treatment regimens based on (i) the pentavalent antimonial (SbV) N-methyl meglumine antimoniate (Glucantime), (ii) the vaccine Leishvacin, or (iii) SbV in association with the vaccine. Comparative analyses of peripheral mononuclear cells prior to and after treatment revealed that the therapeutic regimens induced no significant differences in the percentages of CD3+ and CD4+ T lymphocytes, CD19+ B lymphocytes, or CD16+ and CD56+ natural killer cells. Additionally, the CD4/CD8 and CD3/CD19 ratios remained unaltered by any of the treatments applied. Most previous studies in the field have focused on the analysis of peripheral blood from ACL patients following in vitro stimulation with either Leishmania antigens or mitogens. The ex vivo cellular immune phenotypic profiles determined in the present study, however, revealed that different ACL treatments did not significantly alter either the immune response exhibited by a patient prior to therapy or the expected cure rate.
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Bis(tetra-phenyl-phospho-nium) tris-[N-(methyl-sulfon-yl)dithio-carbimato(2-)-?S,S]stannate(IV).
Acta Crystallogr Sect E Struct Rep Online
PUBLISHED: 07-01-2009
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In the title complex, (C(24)H(20)P)(2)[Sn(C(2)H(3)NO(2)S(3))(3)], the Sn(IV) atom is coordinated by three N-(methyl-sulfon-yl)dithio-carbimate bidentate ligands through the anionic S atoms in a slightly distorted octa-hedral coordination geometry. There is one half-mol-ecule in the asymmetric unit; the complex is located on a crystallographic twofold rotation axis passing through the cation and bis-ecting one of the (non-symmetric) ligands, which appears thus disordered over two sites of equal occupancy. In the crystal structure, weak inter-molecular C-H?O and C-H?S inter-actions contribute to the packing stabilization.
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Human helminth co-infection: no evidence of common genetic control of hookworm and Schistosoma mansoni infection intensity in a Brazilian community.
Int. J. Parasitol.
PUBLISHED: 06-16-2009
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Strong statistical associations between soil-transmitted helminths and schistosomes are frequently observed in co-endemic human populations, although the underlying explanations remain poorly understood. This study investigates the contribution of host genetics and domestic environment to hookworm and Schistosoma mansoni infection intensity and evaluates the role of genetic and non-genetic factors in co-variation of infection intensity. Detailed genealogical information allowed assignment of 1303 individuals living in the Brazilian community of Americaninhas, Minas Gerais state, to 25 pedigrees (containing between two and 1159 members) residing in 303 households. The prevalence of co-infection with both hookworms and schistosomes was high (38.5%), with significant correlation between Necator americanus and S. mansoni faecal egg counts. Bivariate variance component analysis demonstrated a modest but significant species-specific heritability for intensity of N. americanus (h(2)=0.196) and S. mansoni infection (h(2)=0.230). However, after accounting for demographic, socio-economic and household risk factors, no evidence for common genetic control of intensity of hookworm and schistosome infection was observed. There was some evidence for residual clustering within households but the majority (63%) of the covariance between N. americanus and S. mansoni infection intensity remained specific to the individual and could not be explained by shared genes, shared environment or other shared demographic, socio-economic or environmental risk factors. Our results emphasize the importance of exposure to hookworm and schistosome infection in driving the association between levels of infection with these species in hosts resident in areas of high transmission and suggest that much of this common exposure occurs outside the home.
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Synthesis and analgesic profile of conformationally constrained N-acylhydrazone analogues: discovery of novel N-arylideneamino quinazolin-4(3H)-one compounds derived from natural safrole.
Bioorg. Med. Chem.
PUBLISHED: 06-08-2009
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In this work we reported the synthesis and evaluation of the analgesic, anti-inflammatory, and platelet anti-aggregating properties of new 3-(arylideneamino)-2-methyl-6,7-methylenedioxy-quinazolin-4(3H)-one derivatives (3a-j), designed as conformationally constrained analogues of analgesic 1,3-benzodioxolyl-N-acylhydrazones (1) previously developed at LASSBio. Target compounds were synthesized in very good yields exploiting abundant Brazilian natural product safrole (2) as starting material. The pharmacological assays lead us to identify compounds LASSBio-1240 (3b) and LASSBio-1272 (3d) as new analgesic prototypes, presenting an antinociceptive profile more potent and effective than dipyrone and indomethacin used, respectively, as standards in AcOH-induced abdominal constrictions assay and in the formalin test. These results confirmed the success in the exploitation of conformation restriction strategy for identification of novel cyclic N-acylhydrazone analogues with optimized analgesic profile.
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Accurate measurement of the dispersion of hollow-core fibers using a scalable technique.
Opt Express
PUBLISHED: 05-26-2009
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A scalable and accurate technique for measuring the group index and dispersion of optical fibers is used to provide the first accurate measurements of dispersion slope in hollow-core photonic band-gap fibers. We present data showing group index, group-velocity dispersion and dispersion slope in hollow-core fibers guiding at both 800 nm and 1064 nm wavelength.
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Back to the future in Chagas disease: from animal models to patient cohort studies, progress in immunopathogenesis research.
Mem. Inst. Oswaldo Cruz
PUBLISHED: 05-20-2009
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Despite the wealth of information generated by trans-disciplinary research in Chagas disease, knowledge about its multifaceted pathogenesis is still fragmented. Here we review the body of experimental studies in animal models supporting the concept that persistent infection by Trypanosoma cruzi is crucial for the development of chronic myocarditis. Complementing this review, we will make an effort to reconcile seemingly contradictory results concerning the immune profiles of chronic patients from Argentina and Brazil. Finally, we will review the results of molecular studies suggesting that parasite-induced inflammation and tissue damage is, at least in part, mediated by the activities of trans-sialidase, mucin-linked lipid anchors (TLR2 ligand) and cruzipain (a kinin-releasing cysteine protease). One hundred years after the discovery of Chagas disease, it is reassuring that basic and clinical research tends to converge, raising new perspectives for the treatment of chronic Chagas disease.
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Characterization of the presence and distribution of Foxp3(+) cells in chagasic patients with and without megacolon.
Hum. Immunol.
PUBLISHED: 05-13-2009
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Patients with Chagass disease in the chronic phase regularly present with the chagasic megacolon. This form is characterized by inflammation, neuronal destruction, and organ dilatation. Chagasic patients with megacolon always present with inflammatory process near the enteric plexuses of the colon, as previously demonstrated. The aim of this study is to characterize the presence and distribution of Foxp3(+) cells in the muscle layers and neuronal plexuses area of the colon from chagasic patients with and without megacolon. Our results demonstrated that chagasic patients without megacolon presented with an increased concentration of Foxp3(+) cells in all colon layers compared with chagasic patients with megacolon and noninfected individuals. These cells were situated mainly near the blood vessels and rarely were associated with the inflammatory foci. We believe that the presence of Foxp3(+) cells may help to control the inflammatory process through the management of lymphocyte migration and, consequently, prevent neuronal destruction and chagasic megacolon development.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.