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1.
Gen Comp Endocrinol ; 352: 114492, 2024 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-38479678

RESUMO

Individual-level assessments of wild animal health, vital rates, and foraging ecology are critical for understanding population-wide impacts of exposure to stressors. Large whales face multiple stressors, including, but not limited to, ocean noise, pollution, and ship strikes. Because baleen is a continuously growing keratinized structure, serial extraction, and quantification of hormones and stable isotopes along the length of baleen provide a historical record of whale physiology and foraging ecology. Furthermore, baleen analysis enables the investigation of dead specimens, even decades later, allowing comparisons between historic and modern populations. Here, we examined baleen of five sub-adult gray whales and observed distinct patterns of oscillations in δ15N values along the length of their baleen plates which enabled estimation of baleen growth rates and differentiation of isotopic niche widths of the whales during wintering and summer foraging. In contrast, no regular patterns were apparent in δ13C values. Prolonged elevation of cortisol in four individuals before death indicates that chronic stress may have impacted their health and survival. Triiodothyronine (T3) increased over months in the whales with unknown causes of death, simultaneous with elevations in cortisol, but both hormones remained stable in the one case of acute death attributed to killer whale predation. This parallel elevation of cortisol and T3 challenges the classic understanding of their interaction and might relate to increased energetic demands during exposure to stressors. Reproductive hormone profiles in subadults did not show cyclical trends, suggesting they had not yet reached sexual maturity. This study highlights the potential of baleen analysis to retrospectively assess gray whales' physiological status, exposure to stressors, reproductive status, and foraging ecology in the months or years leading up to their death, which can be a useful tool for conservation diagnostics to mitigate unusual mortality events.


Assuntos
Endocrinologia , Baleias , Animais , Hidrocortisona , Estudos Longitudinais , Estudos Retrospectivos
2.
Mem Inst Oswaldo Cruz ; 119: e230181, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38324880

RESUMO

BACKGROUND: In Brazil, transmission of visceral and cutaneous leishmaniasis has expanded geographically over the last decades, with both clinical forms occurring simultaneously in the same area. OBJECTIVES: This study characterised the clinical, spatial, and temporal distribution, and performed entomological surveillance and natural infection analysis of a leishmaniasis-endemic area. METHODS: In order to characterise the risk of leishmaniasis transmission in Altos, Piauí, we described the clinical and socio-demographic variables and the spatial and temporal distribution of cases of American visceral leishmaniasis (AVL) and American cutaneous leishmaniasis (ACL) cases and identified potential phlebotomine vectors. FINDINGS: The urban area concentrated almost 54% of ACL and 86.8% of AVL cases. The temporal and spatial distribution of AVL and ACL cases in Altos show a reduction in the number of risk areas, but the presence of permanent disease transmission foci is observed especially in the urban area. 3,808 phlebotomine specimens were captured, with Lutzomyia longipalpis as the most frequent species (98.45%). Of the 35 females assessed for natural infection, one specimen of Lu. longipalpis tested positive for the presence of Leishmania infantum and Leishmania braziliensis DNA. MAIN CONCLUSION: Our results indicate the presence of risk areas for ACL and AVL in the municipality of Altos and highlight the importance of entomological surveillance to further understand a possible role of Lu. longipalpis in ACL transmission.


Assuntos
Leishmania infantum , Leishmaniose Cutânea , Leishmaniose Visceral , Animais , Feminino , Brasil/epidemiologia , Insetos Vetores/genética , Leishmaniose Cutânea/epidemiologia , Leishmaniose Visceral/epidemiologia , Leishmania infantum/genética , DNA
3.
Oecologia ; 201(2): 397-408, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36650314

RESUMO

Populations usually considered foraging generalists may include specialized individuals that feed on a restricted subset of the prey spectrum consumed by the population. By analyzing the time series of δ13C and δ15N values in sequential growth layer groups within tooth dentin, we measured population- and individual-level variation in resource use of three populations of Guiana dolphins (Sotalia guianensis)-Caravelas River, Babitonga Bay, and Norte Bay-along a latitudinal gradient in the southwestern Atlantic Ocean. We show that the Guiana dolphin at Caravelas River is a generalist population consisting of individual dietary specialists, likely due to the absence of other resident dolphin populations thus allowing individuals to target prey across a wide range of habitats. The Babitonga Bay population is also composed of individual specialists potentially due to the selective foraging behavior of some individuals on high-quality prey sources within and near the bay. In contrast, the Norte Bay population comprises individual generalists, which likely reflects its distinctive cohesive social organization, coexistence with two other dolphin species, and an opportunistic foraging strategy in response to resource fluctuations inherent to the southern limit of the species distribution. Although the Guiana dolphin is generally considered to be a dietary generalist at the population level, our findings reveal that the total niche width of populations and the degree of individual diet specialization are highly context dependent, suggesting dietary plasticity that may be related to a latitudinal gradient in resource availability and environmental conditions.


Assuntos
Golfinhos , Animais , Ecossistema , Dieta , Fatores de Tempo
4.
Parasite Immunol ; 44(11): e12947, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36057920

RESUMO

The golden hamster (Mesocricetus auratus) is commonly used as a promising model for Leishmania braziliensis infection developing skin-ulcerated lesions. However, different protocols using high concentration of parasites inoculated in the footpad result in severe clinical disease. Here, we further investigate the outcome of the site of infection and concentration of L. braziliensis parasites inoculated on the immunopathogenesis and clinical evolution. Initially, hamsters were infected in the ear dermis or hind footpad with a concentration of 1 × 105 parasites. Animals infected in the ear dermis developed a disease, with an increased parasite load that more closely resembled human cutaneous leishmaniasis lesions comparing to the group infected in the footpad. Next, we evaluated if different parasite concentrations (104 , 105 and 106 ) inoculated in the ear dermis would impact the course and clinical aspects of infection. Hamsters infected with 104 and 105 parasites developed mild lesions compared to the group infected with 106 that presented severe and persistent lesions. The parasite load varied between the different parasite concentrations. The inflammatory response was more intense when infection was initiated with 106 parasites accompanied by an increased initial expression of IL-4, IL-10 and arginase in the lymph node followed by expression of both pro-and anti-inflammatory cytokines comparing to groups infected with 104 and 105 parasites. In conclusion, the number of parasites inoculated, and the initial site of infection could influence the inflammatory response, and clinical presentation. Our results suggest that the ear dermis infection model induces a chronic disease that relates to immunopathological aspects of CL natural infection.


Assuntos
Leishmania braziliensis , Leishmaniose Cutânea , Animais , Arginase , Cricetinae , Citocinas , Derme/patologia , Modelos Animais de Doenças , Humanos , Interleucina-10 , Interleucina-4 , Leishmaniose Cutânea/parasitologia , Mesocricetus
5.
Parasite Immunol ; 43(3): e12805, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33131089

RESUMO

Leishmania braziliensis is the main causative agent of American tegumentary leishmaniasis in Brazil. Current treatment includes different drugs that have important side effects and identification of cases of parasite resistance to treatment support the search for new therapeutic strategies. Recent findings have indicated that CXCL10, a chemokine that recruits and activates Th1 cells, NK cells, macrophages, dendritic cells and B lymphocytes, is a potential alternative to treat Leishmania infection. Here, we tested CXCL10 immunotherapy against experimental infection caused by an antimony-resistant isolate of Leishmania braziliensis. Following infection, mice were treated with CXCL10 for 7 days after onset of lesions. We demonstrate that mice treated with CXCL10 controlled lesion progression and parasite burden more efficiently comparing to controls. An increased IFN-γ, IL-10, TGF-ß and low IL-4 production combined with a distinct inflammatory infiltrate composed by activated macrophages, lymphocytes and granulomas was observed in the CXCL10-treated group comparing to controls. However, CXCL10 and Glucantime combined therapy did not improve CXCL10-induced protective effect. Our findings reinforce the potential of CXCL10 immunotherapy as an alternative treatment against infection caused by L. braziliensis resistant to conventional chemotherapy.


Assuntos
Quimiocina CXCL10/uso terapêutico , Fatores Imunológicos/uso terapêutico , Leishmania braziliensis/efeitos dos fármacos , Leishmaniose Cutânea/tratamento farmacológico , Leishmaniose Cutânea/parasitologia , Animais , Antimônio/farmacologia , Brasil , Feminino , Interleucina-10/imunologia , Leishmania braziliensis/imunologia , Leishmania braziliensis/isolamento & purificação , Leishmaniose Cutânea/imunologia , Macrófagos/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Óxido Nítrico/farmacologia , Células Th1/imunologia
6.
J Infect Dis ; 213(11): 1752-61, 2016 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-26768257

RESUMO

Canine leishmaniasis (CanL) is a chronic fatal disease of dogs and a major source of human infection through propagation of parasites in vectors. Here, we infected 8 beagles through multiple experimental vector transmissions with Leishmania infantum-infected Lutzomyia longipalpis. CanL clinical signs varied, although live parasites were recovered from all dog spleens. Splenic parasite burdens correlated positively with Leishmania-specific interleukin 10 levels, negatively with Leishmania-specific interferon γ and interleukin 2 levels, and negatively with Leishmania skin test reactivity. A key finding was parasite persistence for 6 months in lesions observed at the bite sites in all dogs. These recrudesced following a second transmission performed at a distal site. Notably, sand flies efficiently acquired parasites after feeding on lesions at the primary bite site. In this study, controlled vector transmissions identify a potentially unappreciated role for skin at infectious bite sites in dogs with CanL, providing a new perspective regarding the mechanism of Leishmania transmissibility to vector sand flies.


Assuntos
Doenças do Cão/parasitologia , Insetos Vetores/parasitologia , Leishmania infantum , Leishmaniose Visceral/veterinária , Psychodidae/parasitologia , Animais , Reservatórios de Doenças/veterinária , Doenças do Cão/imunologia , Doenças do Cão/patologia , Doenças do Cão/transmissão , Cães , Feminino , Humanos , Imunidade Celular , Imunidade Humoral , Mordeduras e Picadas de Insetos/parasitologia , Mordeduras e Picadas de Insetos/patologia , Mordeduras e Picadas de Insetos/veterinária , Interferon gama/metabolismo , Leishmania infantum/isolamento & purificação , Leishmaniose Visceral/parasitologia , Leishmaniose Visceral/patologia , Leishmaniose Visceral/transmissão , Pele/parasitologia , Baço/parasitologia
7.
J Immunol ; 189(4): 1535-9, 2012 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-22798673

RESUMO

The environmental factors that contribute to the development of autoimmune diseases are largely unknown. Endemic pemphigus foliaceus in humans, known as Fogo Selvagem (FS) in Brazil, is mediated by pathogenic IgG4 autoantibodies against desmoglein 1 (Dsg1). Clusters of FS overlap with those of leishmaniasis, a disease transmitted by sand fly (Lutzomyia longipalpis) bites. In this study, we show that salivary Ags from the sand fly, and specifically the LJM11 salivary protein, are recognized by FS Abs. Anti-Dsg1 monoclonal autoantibodies derived from FS patients also cross-react with LJM11. Mice immunized with LJM11 generate anti-Dsg1 Abs. Thus, insect bites may deliver salivary Ags that initiate a cross-reactive IgG4 Ab response in genetically susceptible individuals and lead to subsequent FS. Our findings establish a clear relationship between an environmental, noninfectious Ag and the development of potentially pathogenic autoantibodies in an autoimmune disease.


Assuntos
Autoanticorpos/imunologia , Reações Cruzadas , Mordeduras e Picadas de Insetos/complicações , Pênfigo/imunologia , Psychodidae/imunologia , Animais , Especificidade de Anticorpos , Autoantígenos/imunologia , Brasil , Ensaio de Imunoadsorção Enzimática , Humanos , Imunoprecipitação , Mordeduras e Picadas de Insetos/epidemiologia , Mordeduras e Picadas de Insetos/imunologia , Camundongos , Glândulas Salivares/imunologia
8.
Front Immunol ; 15: 1335307, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38633260

RESUMO

Introduction: Cutaneous leishmaniasis is a neglected vector-borne parasitic disease prevalent in 92 countries with approximately one million new infections annually. Interactions between vector saliva and the human host alter the response to infection and outcome of disease. Methods: To characterize the human immunological responses developed against saliva of Phlebotomus duboscqi, a Leishmania major (L. major) vector, we repeatedly exposed the arms of 14 healthy U.S volunteers to uninfected P. duboscqi bites. Blood was collected a week after each exposure and used to assess total IgG antibodies against the proteins of P. duboscqi salivary gland homogenate (SGH) and the levels of IFN-gamma and IL-10 from peripheral blood mononuclear cells (PBMCs) stimulated with SGH or recombinant sand fly proteins. We analyzed skin punch biopsies of the human volunteer arms from the insect bite site and control skin site after multiple P. duboscqi exposures (four volunteers) using immunohistochemical staining. Results: A variety of immediate insect bite skin reactions were observed. Late skin reactions to insect bites were characterized by macular hyperpigmentation and/or erythematous papules. Hematoxylin and eosin staining showed moderate mononuclear skin infiltrate with eosinophils in those challenged recently (within 2 months), eosinophils were not seen in biopsies with recall challenge (6 month post bites). An increase in plasma antigen-specific IgG responses to SGH was observed over time. Western Blot results showed strong plasma reactivity to five P. duboscqi salivary proteins. Importantly, volunteers developed a cellular immunity characterized by the secretion of IFN-gamma upon PBMC stimulation with P. duboscqi SGH and recombinant antigens. Discussion: Our results demonstrate that humans mounted a local and systemic immune response against P. duboscqi salivary proteins. Specifically, PduM02/SP15-like and PduM73/adenosine deaminase recombinant salivary proteins triggered a Th1 type immune response that might be considered in future development of a potential Leishmania vaccine.


Assuntos
Mordeduras e Picadas de Insetos , Phlebotomus , Animais , Humanos , Phlebotomus/parasitologia , Leucócitos Mononucleares , Imunidade Celular , Antígenos , Imunoglobulina G , Proteínas e Peptídeos Salivares
9.
J Phys Act Health ; 21(7): 717-725, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38663845

RESUMO

BACKGROUND: To evaluate the influence of previous physical activity (PA) during childhood, adolescence, and current PA practice on the production of antibodies and inflammatory response between the first and second doses of the COVID-19 vaccine. METHODS: Fifty-nine men and 56 women were evaluated before the first vaccine, and 12 weeks later, blood samples were taken to quantify production of anti-severe acute respiratory syndrome coronavirus-2 immunoglobulin G antibodies and cytokines. Previous PA during childhood and adolescence was self-referred, and current PA was assessed using the International Physical Activity Questionnaire. RESULTS: A positive and significant association was observed only between PA practice during adolescence and an increase in antibody production in adulthood (ß = 2012.077, 95% confidence interval, 257.7953-3766.358, P = .025). Individuals who practiced PA during adolescence showed higher production of antibodies between the first and second vaccine dose compared to nonpractitioners (P = .025) and those that accumulated ≥150 minutes per week of current moderate-vigorous PA (MVPA), and presented higher antibody production in relation to who did <150 minutes per week of MVPA (P = .046). Individuals that were practitioners during childhood produced higher G-CSF (P = .047), and those that accumulated ≥150 minutes per week of current MVPA demonstrated lower IP-10 levels (P = .033). However, PA practitioners during adolescence presented higher G-CSF (P = .025), IL-17 (P = .038), IL-1RA (P = .005), IL-1ß (P = .020), and IL-2 (P = .026) levels. CONCLUSION: Our results suggest that adults that accumulated at least 150 minutes of MVPA per week or practiced PA during adolescence developed an improved immune and inflammatory response against COVID-19 vaccination.


Assuntos
Anticorpos Antivirais , COVID-19 , Exercício Físico , SARS-CoV-2 , Humanos , Masculino , Feminino , COVID-19/prevenção & controle , COVID-19/imunologia , Adulto , Adolescente , Anticorpos Antivirais/sangue , SARS-CoV-2/imunologia , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/administração & dosagem , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Citocinas/sangue , Criança , Pessoa de Meia-Idade , Adulto Jovem , Inflamação/imunologia , Fatores Etários
10.
Arterioscler Thromb Vasc Biol ; 32(9): 2185-98, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22796577

RESUMO

OBJECTIVE: Blood-sucking arthropods' salivary glands contain a remarkable diversity of antihemostatics. The aim of the present study was to identify the unique salivary anticoagulant of the sand fly Lutzomyia longipalpis, which remained elusive for decades. METHODS AND RESULTS: Several L. longipalpis salivary proteins were expressed in human embryonic kidney 293 cells and screened for inhibition of blood coagulation. A novel 32.4-kDa molecule, named Lufaxin, was identified as a slow, tight, noncompetitive, and reversible inhibitor of factor Xa (FXa). Notably, Lufaxin's primary sequence does not share similarity to any physiological or salivary inhibitors of coagulation reported to date. Lufaxin is specific for FXa and does not interact with FX, Dansyl-Glu-Gly-Arg-FXa, or 15 other enzymes. In addition, Lufaxin blocks prothrombinase and increases both prothrombin time and activated partial thromboplastin time. Surface plasmon resonance experiments revealed that FXa binds Lufaxin with an equilibrium constant ≈3 nM, and isothermal titration calorimetry determined a stoichiometry of 1:1. Lufaxin also prevents protease-activated receptor 2 activation by FXa in the MDA-MB-231 cell line and abrogates edema formation triggered by injection of FXa in the paw of mice. Moreover, Lufaxin prevents FeCl(3)-induced carotid artery thrombus formation and prolongs activated partial thromboplastin time ex vivo, implying that it works as an anticoagulant in vivo. Finally, salivary gland of sand flies was found to inhibit FXa and to interact with the enzyme. CONCLUSIONS: Lufaxin belongs to a novel family of slow-tight FXa inhibitors, which display antithrombotic and anti-inflammatory activities. It is a useful tool to understand FXa structural features and its role in prohemostatic and proinflammatory events.


Assuntos
Anti-Inflamatórios/farmacologia , Inibidores do Fator Xa , Fibrinolíticos/farmacologia , Inflamação/prevenção & controle , Proteínas de Insetos/farmacologia , Psychodidae/química , Receptor PAR-2/antagonistas & inibidores , Glândulas Salivares/química , Trombose/prevenção & controle , Sequência de Aminoácidos , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Coagulação Sanguínea/efeitos dos fármacos , Calorimetria , Linhagem Celular Tumoral , Cloretos , Clonagem Molecular , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Fator Xa/metabolismo , Feminino , Compostos Férricos , Fibrinolíticos/química , Fibrinolíticos/isolamento & purificação , Células HEK293 , Humanos , Inflamação/sangue , Inflamação/metabolismo , Proteínas de Insetos/química , Proteínas de Insetos/isolamento & purificação , Camundongos , Camundongos Endogâmicos C57BL , Dados de Sequência Molecular , Peso Molecular , Tempo de Tromboplastina Parcial , Ligação Proteica , Tempo de Protrombina , Ratos , Receptor PAR-2/metabolismo , Proteínas Recombinantes/antagonistas & inibidores , Proteínas Recombinantes/metabolismo , Ressonância de Plasmônio de Superfície , Tromboplastina/antagonistas & inibidores , Tromboplastina/metabolismo , Trombose/sangue , Trombose/induzido quimicamente , Trombose/metabolismo , Fatores de Tempo
11.
Mar Environ Res ; 184: 105857, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36577309

RESUMO

We analyzed δ13C and δ15N values in different tooth portions (Growth Layer Groups, GLGs) of franciscanas, Pontoporia blainvillei, to investigate their effect on whole tooth (WT) isotopic values and the implications for dietary estimates. Tooth portions included the dentin deposited during the prenatal development (PND), the first year of life (GLG1) deposited during the nursing period and the central part of the tooth with no distinction amongst subsequent GLGs (Center). Isotopic mixing models estimating the contribution of PND, GLG1 and Center to WT showed that GLG1 has a strong effect on WT isotope values in juveniles, while Center only starts to affect WT isotopic values from age four. Isotopic mixing models estimating prey contribution to the diet of juveniles using WT vs Center tooth portions significantly differed in dietary outputs, demonstrating that GLG1 influence on WT isotope values affects dietary estimates in young franciscanas. As the small tooth size and narrowness of the last GLGs hinder the analysis of individual layers, we recommend excluding GLG1 in studies based on teeth isotope composition in franciscanas and caution when interpreting isotopic values from the WT of other small cetaceans.


Assuntos
Golfinhos , Animais , Isótopos de Carbono , Isótopos de Nitrogênio , Dieta , Cetáceos , Viés
12.
J Epidemiol Community Health ; 77(6): 410-416, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37116960

RESUMO

BACKGROUND: The Tabora Maternal and Newborn Health Initiative project was a multicomponent intervention to improve maternal and newborn health in the Tabora region of Tanzania. Components included training healthcare providers and community health workers, infrastructure upgrades, and improvements to health management. This study aimed to examine the impact of trainings on four key outcomes: skilled birth attendance, antenatal care, respectful maternity care and patient-provider communication. METHODS: Trainings were delivered sequentially at four time points between 2018 and 2019 in eight districts (two districts at a time). Cross-sectional surveys were administered to a random sample of households in all districts at baseline and after each training wave. Due to practical necessities, the original stepped wedge cluster randomised design of the evaluation was altered mid-programme. Therefore, a difference-in-differences for multiple groups in multiple periods was adopted to compare outcomes in treated districts to not yet treated districts. Risk differences were estimated for the overall average treatment effect on the treated and group/time dynamic effects. RESULTS: Respondents reported 3895 deliveries over the course of the study. The intervention was associated with a 12.9 percentage point increase in skilled birth attendance (95% CI 0.4 to 25.4), which began to increase 4 months after the end of training in each district. There was little evidence of impact on antenatal care visits, respectful treatment during delivery and patient-provider communication. CONCLUSION: Interventions to train local healthcare workers in basic and comprehensive emergency obstetric and newborn care increased skilled birth attendance but had limited impact on other pregnancy-related outcomes.


Assuntos
Serviços de Saúde Materna , Recém-Nascido , Criança , Gravidez , Feminino , Humanos , Tanzânia , Saúde da Criança , Estudos Transversais , Cuidado Pré-Natal
13.
Hydrobiologia ; 850(12-13): 2611-2653, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37323646

RESUMO

In this review we highlight the relevance of biodiversity that inhabit coastal lagoons, emphasizing how species functions foster processes and services associated with this ecosystem. We identified 26 ecosystem services underpinned by ecological functions performed by bacteria and other microbial organisms, zooplankton, polychaetae worms, mollusks, macro-crustaceans, fishes, birds, and aquatic mammals. These groups present high functional redundancy but perform complementary functions that result in distinct ecosystem processes. Because coastal lagoons are located in the interface between freshwater, marine and terrestrial ecosystems, the ecosystem services provided by the biodiversity surpass the lagoon itself and benefit society in a wider spatial and historical context. The species loss in coastal lagoons due to multiple human-driven impacts affects the ecosystem functioning, influencing negatively the provision of all categories of services (i.e., supporting, regulating, provisioning and cultural). Because animals' assemblages have unequal spatial and temporal distribution in coastal lagoons, it is necessary to adopt ecosystem-level management plans to protect habitat heterogeneity and its biodiversity, ensuring the provision of services for human well-being to multi-actors in the coastal zone.

14.
PLoS Negl Trop Dis ; 17(6): e0011388, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37276231

RESUMO

BACKGROUND: Leishmaniases are vector borne diseases caused by Leishmania spp. parasites transmitted by female sandflies (Diptera: Psychodidae) whose geographic distribution is influenced by environmental factors. Among the main tools for studying the distribution of vector species, modeling techniques are used to analyze the influence of climatic and environmental factors on the distribution of these insects and their association with human cases of the disease. METHODOLOGY/PRINCIPAL FINDINGS: Here, we used a multiscale ecological niche modeling approach to assess the environmental suitability of sandfly vectors of the etiological agents of Visceral (VL) and American Cutaneous Leishmaniasis (ACL) in Piauí state, northeastern Brazil, and then evaluated their relationship with human disease incidence. For this, we obtained the geographic coordinates of the vector species Lutzomyia longipalpis and Nyssomyia whitmani through literature review, online databases and unpublished records. These data were used for the development of predictive models of the distribution of both sandflies species based on climatic and environmental variables. Finally, the environmental suitability for the presence of these vectors was compared with the incidence of both the diseases at the municipality level. The final models for each sandfly species showed good predictive powers with performance metric values of 0.889 for Lu. longipalpis and 0.776 for Ny. whitmani. The areas with greater environmental suitability for the presence of these species were concentrated in the central-north region of Piauí and coincide with the location of those municipalities presenting higher incidences of VL and ACL, situated in the central-north and extreme north of the state, respectively. The south and southeast regions of Piauí state have low incidence of these diseases and presented low environmental suitability for the presence of both vectors. CONCLUSIONS/SIGNIFICANCE: We discuss how predictive modeling can guide entomological and epidemiological surveillances and recommend an increased supervision and control activities in Teresina (capital of the state of Piaui), Altos and Pedro II, in addition to other municipalities with similar social and environmental characteristics.


Assuntos
Leishmaniose Cutânea , Phlebotomus , Psychodidae , Animais , Feminino , Humanos , Incidência , Brasil/epidemiologia , Insetos Vetores/parasitologia , Leishmaniose Cutânea/parasitologia , Psychodidae/parasitologia
15.
PLoS One ; 18(11): e0287665, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38011211

RESUMO

Treatment of cutaneous leishmaniasis depends on drugs that potentially cause serious side effects and resistance. Thus, topical therapies are attractive alternatives to the drugs currently used. 3ß, 6ß, 16ß-trihydroxylup-20 (29)-ene is a lupane triterpene isolated from Combretum leprosum Mart. leaves (CLF-1), with reports of in vitro antileishmanial effect against L. amazonensis and to promote lesion healing in animal model. Herein, we evaluated the in vitro and in vivo antileishmanial and healing effects of CLF-1 against L. braziliensis. CLF-1 treatment showed low toxicity in macrophages and significantly reduced parasite load in vitro. CLF-1 induced higher IL-12 and TNF-α production and more discrete IL-4 and IL-10 production. For in vivo evaluation, a CLF-1 cream formulation was prepared to treat hamsters infected with L. braziliensis. CLF-1 treatment was able to reduce parasite load of the infected skin and lymph node more efficiently than the conventional treatment. Histopathological analysis indicated a strong inflammatory response accompanied by an important healing response. Data from this study indicate that topical CLF-1 treatment was effective and non-toxic in L. braziliensis infected hamsters suggesting its potential for further development as a future therapeutic intervention.


Assuntos
Antiprotozoários , Combretum , Leishmania braziliensis , Leishmaniose Cutânea , Cricetinae , Animais , Camundongos , Pele/patologia , Leishmaniose Cutânea/tratamento farmacológico , Leishmaniose Cutânea/patologia , Cicatrização , Antiprotozoários/farmacologia , Antiprotozoários/uso terapêutico , Camundongos Endogâmicos BALB C
16.
J Biol Chem ; 286(37): 32383-93, 2011 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-21795673

RESUMO

LJM11, an abundant salivary protein from the sand fly Lutzomyia longipalpis, belongs to the insect "yellow" family of proteins. In this study, we immunized mice with 17 plasmids encoding L. longiplapis salivary proteins and demonstrated that LJM11 confers protective immunity against Leishmania major infection. This protection correlates with a strong induction of a delayed type hypersensitivity (DTH) response following exposure to L. longipalpis saliva. Additionally, splenocytes of exposed mice produce IFN-γ upon stimulation with LJM11, demonstrating the systemic induction of Th1 immunity by this protein. In contrast to LJM11, LJM111, another yellow protein from L. longipalpis saliva, does not produce a DTH response in these mice, suggesting that structural or functional features specific to LJM11 are important for the induction of a robust DTH response. To examine these features, we used calorimetric analysis to probe a possible ligand binding function for the salivary yellow proteins. LJM11, LJM111, and LJM17 all acted as high affinity binders of prohemostatic and proinflammatory biogenic amines, particularly serotonin, catecholamines, and histamine. We also determined the crystal structure of LJM11, revealing a six-bladed ß-propeller fold with a single ligand binding pocket located in the central part of the propeller structure on one face of the molecule. A hypothetical model of LJM11 suggests a positive electrostatic potential on the face containing entry to the ligand binding pocket, whereas LJM111 is negative to neutral over its entire surface. This may be the reason for differences in antigenicity between the two proteins.


Assuntos
Hipersensibilidade Tardia/imunologia , Proteínas de Insetos/imunologia , Leishmania major/imunologia , Leishmaniose Cutânea/imunologia , Psychodidae/imunologia , Saliva/imunologia , Células Th1/imunologia , Animais , Aminas Biogênicas/imunologia , Feminino , Hipersensibilidade Tardia/genética , Inflamação/genética , Inflamação/imunologia , Proteínas de Insetos/genética , Proteínas de Insetos/farmacologia , Interferon gama/genética , Interferon gama/imunologia , Leishmaniose Cutânea/genética , Leishmaniose Cutânea/prevenção & controle , Camundongos , Estrutura Terciária de Proteína , Psychodidae/genética , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Proteínas Recombinantes/farmacologia
17.
PLoS Pathog ; 5(5): e1000441, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19461875

RESUMO

Immunity to a sand fly salivary protein protects against visceral leishmaniasis (VL) in hamsters. This protection was associated with the development of cellular immunity in the form of a delayed-type hypersensitivity response and the presence of IFN-gamma at the site of sand fly bites. To date, there are no data available regarding the cellular immune response to sand fly saliva in dogs, the main reservoirs of VL in Latin America, and its role in protection from this fatal disease. Two of 35 salivary proteins from the vector sand fly Lutzomyia longipalpis, identified using a novel approach termed reverse antigen screening, elicited strong cellular immunity in dogs. Immunization with either molecule induced high IgG(2) antibody levels and significant IFN-gamma production following in vitro stimulation of PBMC with salivary gland homogenate (SGH). Upon challenge with uninfected or infected flies, immunized dogs developed a cellular response at the bite site characterized by lymphocytic infiltration and IFN-gamma and IL-12 expression. Additionally, SGH-stimulated lymphocytes from immunized dogs efficiently killed Leishmania infantum chagasi within autologous macrophages. Certain sand fly salivary proteins are potent immunogens obligatorily co-deposited with Leishmania parasites during transmission. Their inclusion in an anti-Leishmania vaccine would exploit anti-saliva immunity following an infective sand fly bite and set the stage for a protective anti-Leishmania immune response.


Assuntos
Proteínas de Insetos/imunologia , Leishmania infantum/imunologia , Leishmaniose Visceral/imunologia , Proteínas e Peptídeos Salivares/imunologia , Animais , Formação de Anticorpos , Citocinas/genética , Citocinas/metabolismo , Interpretação Estatística de Dados , Cães , Feminino , Expressão Gênica , Hipersensibilidade Tardia , Imunidade Celular , Mordeduras e Picadas de Insetos/imunologia , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Insetos Vetores/genética , Insetos Vetores/imunologia , Insetos Vetores/parasitologia , Leishmania infantum/fisiologia , Linfócitos/imunologia , Psychodidae/genética , Psychodidae/imunologia , Psychodidae/parasitologia , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Proteínas Recombinantes/metabolismo , Proteínas e Peptídeos Salivares/genética , Proteínas e Peptídeos Salivares/metabolismo , Pele/imunologia
18.
Exp Parasitol ; 127(1): 1-8, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20493843

RESUMO

Nitric oxide (NO) and NO-derived reactive nitrogen species (RNS) are present in the food vacuole (FV) of Plasmodium falciparum trophozoites. The product of PFL1555w, a putative cytochrome b(5), localizes in the FV membrane, similar to what was previously observed for the product of PF13_0353, a putative cytochrome b(5) reductase. These two gene products may contribute to NO generation by denitrification chemistry from nitrate and/or nitrite present in the erythrocyte cytosol. The possible coordination of NO to heme species present in the food vacuole was probed by resonance Raman spectroscopy. The spectroscopic data revealed that in situ generated NO interacts with heme inside the intact FVs to form ferrous heme nitrosyl complexes that influence intra-vacuolar heme solubility. The formation of heme nitrosyl complexes within the FV is a previously unrecognized factor that could affect the equilibrium between soluble and crystallized heme within the FV in vivo.


Assuntos
Heme/metabolismo , Óxido Nítrico/metabolismo , Plasmodium falciparum/metabolismo , Vacúolos/metabolismo , Animais , Cristalização , Eritrócitos/parasitologia , Heme/química , Humanos , Soros Imunes , Immunoblotting , Camundongos , Microscopia de Fluorescência , Plasmodium falciparum/genética , Plasmodium falciparum/ultraestrutura , Solubilidade , Análise Espectral Raman , Vacúolos/química
19.
Proc Natl Acad Sci U S A ; 105(22): 7845-50, 2008 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-18509051

RESUMO

Visceral leishmaniasis (VL) is a fatal disease for humans, and no vaccine is currently available. Sand fly salivary proteins have been associated with protection against cutaneous leishmaniasis. To test whether vector salivary proteins can protect against VL, a hamster model was developed involving intradermal inoculation in the ears of 100,000 Leishmania infantum chagasi parasites together with Lutzomyia longipalpis saliva to mimic natural transmission by sand flies. Hamsters developed classical signs of VL rapidly, culminating in a fatal outcome 5-6 months postinfection. Saliva had no effect on the course of infection in this model. Immunization with 16 DNA plasmids coding for salivary proteins of Lu. longipalpis resulted in the identification of LJM19, a novel 11-kDa protein, that protected hamsters against the fatal outcome of VL. LJM19-immunized hamsters maintained a low parasite load that correlated with an overall high IFN-gamma/TGF-beta ratio and inducible NOS expression in the spleen and liver up to 5 months postinfection. Importantly, a delayed-type hypersensitivity response with high expression of IFN-gamma was also noted in the skin of LJM19-immunized hamsters 48 h after exposure to uninfected sand fly bites. Induction of IFN-gamma at the site of bite could partly explain the protection observed in the viscera of LJM19-immunized hamsters through direct parasite killing and/or priming of anti-Leishmania immunity. We have shown that immunity to a defined salivary protein (LJM19) confers powerful protection against the fatal outcome of a parasitic disease, which reinforces the concept of using components of arthropod saliva in vaccine strategies against vector-borne diseases.


Assuntos
Proteínas de Insetos/imunologia , Insetos Vetores/imunologia , Vacinas contra Leishmaniose/imunologia , Leishmaniose Visceral/prevenção & controle , Psychodidae/imunologia , Proteínas e Peptídeos Salivares/imunologia , Animais , Cricetinae , Modelos Animais de Doenças , Humanos , Imunidade , Mordeduras e Picadas de Insetos/imunologia , Proteínas de Insetos/genética , Insetos Vetores/parasitologia , Interferon gama/metabolismo , Vacinas contra Leishmaniose/uso terapêutico , Leishmaniose Visceral/imunologia , Plasmídeos/genética , Psychodidae/parasitologia , Proteínas e Peptídeos Salivares/genética , Vacinação
20.
Cien Saude Colet ; 26(9): 4309-4320, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34586281

RESUMO

The purpose of this study is to determine the factors associated with negative self-rated health in Brazil. The sample consisted of 5,259 adults from five representative capitals of the five regions of Brazil. Data collection was achieved in the following municipalities: Palmas (North Region), João Pessoa (Northeast Region), Goiânia (Central-West Region), Vitória (Southeast Region) and Florianópolis (South Region). For the analysis of the data, Binary Logistic Regression for determine the factors associated with negative self-rated health was used. Negative self-rated health was identified in 31.43% of Brazilians. The factors that were significantly associated were bad air quality, does not have public spaces for leisure, older age group, insufficient salary to cover expenses, a rare practice of physical exercises, does not perform healthy eating, active commuting for study or employment and commuting time for above 30 minutes, dissatisfaction with health services and still, not working, not looking for a job and finally, reside in some Brazilian regions. The study presents the importance of socioenvironmental and behavioral factors for the self-rated health of Brazilian adults, as well as it shows high rates of negative self-rated health compared to other studies.


Assuntos
Exercício Físico , Atividades de Lazer , Adulto , Idoso , Brasil , Cidades , Estudos Transversais , Humanos , Modelos Logísticos , Fatores Socioeconômicos
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