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1.
Environ Sci Pollut Res Int ; 31(32): 45177-45191, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38961017

ABSTRACT

The intensification of livestock farming can pose risks to the environment due to the increased use of veterinary products and the generation of waste in confined areas. The quality of water bodies near livestock establishments (Areco River (A) and Doblado stream (D), San Antonio de Areco, Buenos Aires, Argentina) was studied by physicochemical parameters, metals, pesticides, emerging contaminants, and lethal and sublethal toxicity (neurotoxicity and oxidative stress) in larvae of the native amphibian Rhinella arenarum. Six sites were selected: upstream (S1A and S1D), at the level (S2A and S2D), and downstream (S3A and S3D) from the establishments. A low concentration of dissolved oxygen was observed in Doblado stream (< 2.34 mg/L). Cu, Mn, V, and Zn exceeded the limits for the protection of aquatic life at various sites. Between 24 and 34 pesticides were detected in all sites, with 2,4-D, atrazine, and metolachlor being the most recurrent. In water and sediment, the concentrations of ivermectin (S2A, 1.32 µg/L and 58.18 µg/kg; S2D, 0.8 µg/L and 85.22 µg/kg) and oxytetracycline (S2A, < 1 mg/L and < 1 mg/kg; S2D, 11.8 mg/L and 39 mg/kg) were higher at sites near the establishments. All sites caused between 30 and 38.3% of lethality and produced neurotoxicity and alterations in the reduced glutathione content. Moreover, larvae exposed to samples from all sites incorporated ivermectin. These results demonstrate the degradation of the studied sites in relation to the agricultural activities of the area, highlighting the need to take measures to protect and preserve aquatic ecosystems.


Subject(s)
Agriculture , Ecotoxicology , Environmental Monitoring , Water Pollutants, Chemical , Water Quality , Animals , Water Pollutants, Chemical/analysis , Argentina , Cattle , Pesticides/toxicity
2.
Microbes Infect ; 26(5-6): 105337, 2024.
Article in English | MEDLINE | ID: mdl-38615883

ABSTRACT

The thymus plays a crucial role in T cell differentiation, a complex process influenced by various factors such as antigens, the microenvironment and thymic architecture. The way the thymus resolves infections is critical, as chronic persistence of microbes or inflammatory mediators can obstruct the differentiation. Here, we illustrate that following inflammatory T helper 1 infectious processes like those caused by Candida albicans or Trypanosoma cruzi, single positive thymocytes adopt a mature phenotype. Further investigations focused on T. cruzi infection, reveal a substantial existence of CD44+ cells in both the cortical and medullary areas of the thymus at the onset of infection. This disturbance coincides with heightened interferon gamma (IFNγ) production by thymocytes and an increased cytotoxic capacity against T. cruzi-infected macrophages. Additionally, we observe a reduced exportation capacity in T. cruzi-infected mice. Some alterations can be reversed in IFNγ knockout mice (KO). Notably, the majority of these effects can be replicated by systemic expression of interleukin (IL)-12+IL-18, underlining the predominantly inflammatory rather than pathogen-specific nature of these phenomena. Understanding the mechanisms through which systemic inflammation disrupts normal T cell development, as well as subsequent T cell exportation to secondary lymphoid organs (SLO) is pivotal for comprehending susceptibility to diseases in different pathological scenarios.


Subject(s)
Chagas Disease , Cytokines , Mice, Knockout , Th1 Cells , Thymus Gland , Trypanosoma cruzi , Animals , Chagas Disease/immunology , Chagas Disease/parasitology , Chagas Disease/pathology , Chagas Disease/metabolism , Trypanosoma cruzi/immunology , Mice , Thymus Gland/immunology , Thymus Gland/pathology , Th1 Cells/immunology , Cytokines/metabolism , Interferon-gamma/metabolism , Interferon-gamma/immunology , Mice, Inbred C57BL , Inflammation/immunology , Cell Differentiation
3.
Neuroimmunomodulation ; 31(1): 78-88, 2024.
Article in English | MEDLINE | ID: mdl-38527434

ABSTRACT

BACKGROUND: The brain and the immune systems represent the two primary adaptive systems within the body. Both are involved in a dynamic process of communication, vital for the preservation of mammalian homeostasis. This interplay involves two major pathways: the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system. SUMMARY: The establishment of infection can affect immunoneuroendocrine interactions, with functional consequences for immune organs, particularly the thymus. Interestingly, the physiology of this primary organ is not only under the control of the central nervous system (CNS) but also exhibits autocrine/paracrine regulatory circuitries mediated by hormones and neuropeptides that can be altered in situations of infectious stress or chronic inflammation. In particular, Chagas disease, caused by the protozoan parasite Trypanosoma cruzi (T. cruzi), impacts upon immunoneuroendocrine circuits disrupting thymus physiology. Here, we discuss the most relevant findings reported in relation to brain-thymic connections during T. cruzi infection, as well as their possible implications for the immunopathology of human Chagas disease. KEY MESSAGES: During T. cruzi infection, the CNS influences thymus physiology through an intricate network involving hormones, neuropeptides, and pro-inflammatory cytokines. Despite some uncertainties in the mechanisms and the fact that the link between these abnormalities and chronic Chagasic cardiomyopathy is still unknown, it is evident that the precise control exerted by the brain over the thymus is markedly disrupted throughout the course of T. cruzi infection.


Subject(s)
Brain , Chagas Disease , Thymus Gland , Humans , Chagas Disease/immunology , Chagas Disease/physiopathology , Animals , Brain/immunology , Thymus Gland/immunology , Thymus Gland/physiology , Trypanosoma cruzi/physiology , Trypanosoma cruzi/immunology , Hypothalamo-Hypophyseal System/immunology , Hypothalamo-Hypophyseal System/metabolism , Hypothalamo-Hypophyseal System/physiopathology , Neuroimmunomodulation/physiology , Neuroimmunomodulation/immunology , Pituitary-Adrenal System/immunology , Pituitary-Adrenal System/physiopathology , Pituitary-Adrenal System/metabolism
4.
Pathogens ; 12(12)2023 Dec 14.
Article in English | MEDLINE | ID: mdl-38133333

ABSTRACT

Infection by Brucella species in pregnant animals and humans is associated with an increased risk of abortion, preterm birth, and transmission of the infection to the offspring. The pathogen has a marked tropism for the placenta and the pregnant uterus and has the ability to invade and replicate within cells of the maternal-fetal unit, including trophoblasts and decidual cells. Placentitis is a common finding in infected pregnant animals. Several proinflammatory factors have been found to be increased in both the placenta of Brucella-infected animals and in trophoblasts or decidual cells infected in vitro. As normal pregnancies require an anti-inflammatory placental environment during most of the gestational period, Brucella-induced placentitis is thought to be associated with the obstetric complications of brucellosis. A few studies suggest that the blockade of proinflammatory factors may prevent abortion in these cases.

5.
Water Environ Res ; 95(6): e10899, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37255341

ABSTRACT

Amphibians are subject to several stressors in the aquatic and terrestrial environments, and human activities have profoundly impacted this vertebrate group. The aim of the present study was to analyze physicochemical parameters, metals and pesticide residues, and the toxicity of water and sediment samples from an environment with high agricultural activity (S1: Salto stream; S2: drainage channel downstream from S1) by means of bioassays using Rhinella arenarum (Amphibia: Anura) larvae. Metals and pesticides were analyzed in water and sediment samples by fluorescence spectrometer of X-ray by total reflection and ultra-high-performance liquid chromatography-MS/MS, respectively. For lethality bioassays, 10 larvae (in triplicate) were exposed for 504 h to water and sediment samples. Also, 50 larvae were exposed for 96 h (in triplicate) to water and sediment samples for the evaluation of biomarkers of neurotoxicity, oxidative stress, and genotoxicity. Twenty-six different pesticides (mainly herbicides) were detected in both sites, and Cu, Zn, and Pb exceeded the limit for protection of aquatic life. Lethality was observed in larvae exposed to water and sediment samples from both sites at chronic exposure. Oxidative stress was observed in larvae exposed to both sites. In larvae exposed to samples from S1, alterations in the neurotoxicity biomarkers were observed. These results alert about the degradation of the sites and highlight the need to monitor and control the use of pesticides. PRACTITIONER POINTS: Twenty-six pesticides were detected in water and sediment from Salto stream basin. Significant mortality was observed in larvae exposed to samples from all sites. Sublethal effects were observed mainly in larvae exposed to samples from Salto stream. The degraded quality can be associated with the agricultural activities of the area.


Subject(s)
Pesticides , Water Pollutants, Chemical , Humans , Animals , Water , Water Pollutants, Chemical/analysis , Tandem Mass Spectrometry , Pesticides/analysis , Biomarkers , Amphibians/metabolism , Environmental Monitoring/methods , Geologic Sediments/chemistry
6.
Environ Res ; 226: 115692, 2023 06 01.
Article in English | MEDLINE | ID: mdl-36931378

ABSTRACT

In the Paraná River lower basin, an important agro-productive area of Argentina, crop fields and cattle breeding activities are common and may affect water quality. So, the aim of this study was to analyze the impacts of cattle breeding and agricultural activities on a stream from Buenos Aires, through physicochemical parameters (metals, pesticides, and emerging contaminants) and ecotoxicological parameters with Rhinella arenarum larvae, a native amphibian species. Three sites were selected on an ordinary plain stream that goes through agricultural fields and a cattle breeding establishment (upstream -S1-, near -S2- and downstream -S3- the establishment). Physicochemical parameters were measured in situ (in water) and in laboratory (in water and sediment samples: metals, pesticides, ivermectin and oxytetracycline). A semi-static chronic toxicity bioassay (504 h) was performed with water samples, and neurotoxicity, oxidative stress and genotoxicity biomarkers were measured after acute exposure (96 h). According to the index, a degradation in the water quality was observed in all sites. Ivermectin (8.03 mg/kg) and oxytetracycline (1.9 mg/kg) were detected in sediment samples from S2. Pesticides were detected in all sites, mainly in water samples: S1 presented the highest variability (7 residues) and in S3 AMPA, glyphosate and acetochlor concentrations were higher (10.3, 22.4 and 23.8 µg/L). Also, all sites significantly produced lethality at chronic exposure. Lethality at 504h was 40% for S1, 56.66% for S2 and 93.33% for S3. At acute exposure, the oxidative stress biomarkers were altered on R. arenarum larvae exposed to all sites and the neurotoxicity biomarkers were altered on larvae exposed to S1 and S3. Water quality was severely degraded by the surrounding agricultural and cattle breeding activities, which may represent a threat to the ecosystems.


Subject(s)
Oxytetracycline , Pesticides , Water Pollutants, Chemical , Animals , Cattle , Pesticides/analysis , Ecosystem , Ivermectin , Water Pollutants, Chemical/analysis , Metals , Amphibians/metabolism , Larva/metabolism , Biomarkers , Environmental Monitoring
7.
Acta Trop ; 241: 106889, 2023 May.
Article in English | MEDLINE | ID: mdl-36893830

ABSTRACT

Trypanosoma cruzi, the agent of Chagas disease, can infect through conjunctive or oral mucosas. Therefore, the induction of mucosal immunity by vaccination is relevant not only to trigger local protection but also to stimulate both humoral and cell-mediated responses in systemic sites to control parasite dissemination. In a previous study, we demonstrated that a nasal vaccine based on a Trans-sialidase (TS) fragment plus the mucosal STING agonist c-di-AMP, was highly immunogenic and elicited prophylactic capacity. However, the immune profile induced by TS-based nasal vaccines at the nasopharyngeal-associated lymphoid tissue (NALT), the target site of nasal immunization, remains unknown. Hence, we analyzed the NALT cytokine expression generated by a TS-based vaccine plus c-di-AMP (TSdA+c-di-AMP) and their association with mucosal and systemic immunogenicity. The vaccine was administered intranasally, in 3 doses separated by 15 days each other. Control groups received TSdA, c-di-AMP, or the vehicle in a similar schedule. We demonstrated that female BALB/c mice immunized intranasally with TSdA+c-di-AMP boosted NALT expression of IFN-γ and IL-6, as well as IFN-ß and TGF-ß. TSdA+c-di-AMP increased TSdA-specific IgA secretion in the nasal passages and also in the distal intestinal mucosa. Moreover, T and B-lymphocytes from NALT-draining cervical lymph nodes and spleen showed an intense proliferation after ex-vivo stimulation with TSdA. Intranasal administration of TSdA+c-di-AMP provokes an enhancement of TSdA-specific IgG2a and IgG1 plasma antibodies, accompanied by an increase IgG2a/IgG1 ratio, indicative of a Th1-biased profile. In addition, immune plasma derived from TSdA+c-di-AMP vaccinated mice exhibit in-vivo and ex-vivo protective capacity. Lastly, TSdA+c-di-AMP nasal vaccine also promotes intense footpad swelling after local TSdA challenge. Our data support that TSdA+c-di-AMP nasal vaccine triggers a NALT mixed pattern of cytokines that were clearly associated with an evident mucosal and systemic immunogenicity. These data are useful for further understanding the immune responses elicited by the NALT following intranasal immunization and the rational design of TS-based vaccination strategies for prophylaxis against T. cruzi.


Subject(s)
Chagas Disease , Trypanosoma cruzi , Vaccines , Female , Animals , Mice , Administration, Intranasal , Immunity, Mucosal , Lymph Nodes , Chagas Disease/prevention & control , Cytokines/metabolism , Nasopharynx/metabolism , Intestinal Mucosa/metabolism , Immunoglobulin G , Mice, Inbred BALB C
8.
Aquat Toxicol ; 253: 106342, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36327688

ABSTRACT

The lower Salado River basin receive agricultural, industrial and domestic waste water. So, the aim was to evaluate the quality of three sampling sites that belong to the Salado River basin (S1: Cululú stream; S2: Salado River, at Esperanza City, S3: Salado River at Santo Tomé City) based on physicochemical parameters, metals and pesticides analyses and ecotoxicity on Rhinella arenarum larvae. R. arenarum larvae (Gosner Stage -GS- 25) were chronically exposed (504h) to complex matrixes of surface water and sediment samples of each site for the determination of the survival rate. Biomarkers of oxidative stress, neurotoxicity and genotoxicity were analyzed in R. arenarum larvae (GS. 25) after exposure (96h) to the complex matrix of water and sediment. The water quality index showed a marginal quality for all sites, influenced mainly by low dissolved oxygen, high total suspended solid, phosphate, nitrite, conductivity, Pb, Cr and Cu levels. Metal concentrations were higher in sediment than in water samples (˜34-35000 times). In total, thirty different pesticides were detected in all water and sediment samples, S1 presented the greatest variety (26). Glyphosate and AMPA were detected in sediments from all sites, being higher in S3. N,N-Diethyl-meta-toluamide (DEET) and atrazine were detected in all water samples. Greatest mortality was observed in larvae exposed to samples from S1 from 288h (43.3%), reaching a maximum value of 50% at 408h. Oxidative stress and genotoxicity were observed in larvae exposed to S1 and S3 matrix samples. Neurotoxicity was observed in larvae exposed to all matrix samples. The integrated biomarker response index showed that larvae exposed to S1 and S3 were the most affected. According to the physicochemical data and the ecotoxicity assessment, this important river basin is significantly degraded and may represent a risk to aquatic biota, especially for R. arenarum larvae.


Subject(s)
Pesticides , Water Pollutants, Chemical , Animals , Rivers , Larva , Argentina , Water Pollutants, Chemical/toxicity , Pesticides/analysis , Bufo arenarum , Metals/analysis , Environmental Monitoring , Geologic Sediments/analysis
9.
Article in English | MEDLINE | ID: mdl-35897515

ABSTRACT

Community-academic partnerships (CAPs) are being increasingly used to study and address health disparity issues. CAPs help to create new bodies of knowledge and innovative solutions to community problems, which benefits the community and academia. Supported by a grant, a partnership was formed between an academic research team and a community health organization to analyze and interpret data collected from the caregivers of asthmatic African American children living in urban low-income households. Using a case study approach, we discuss how we built a healthy CAP and the lessons learned from the process. Our analysis was guided by the six main factors that facilitate success in developing collaborative relationships, including (1) environment; (2) membership; (3) process and structure; (4) communication; (5) purpose; and (6) resources. Based on these six factors, we describe our collaboration process, challenges, and areas for improvement. We aimed to provide a "points-to-consider" roadmap for academic and community partners to establish and maintain a mutually beneficial and satisfactory relationship. Collaborating with community members and organizations provides unique opportunities for researchers and students to apply their skills and knowledge from textbooks and the classroom, engage with community members, and improve real-life community needs. Building a constructive CAP involves efforts, energy, and resources from both parties. The six major themes derived from our project offer suggestions for building a healthy, collaborative, and productive relationship that best serves communities in the future.


Subject(s)
Community-Based Participatory Research , Community-Institutional Relations , Child , Humans , Minority Groups , Poverty , Quality of Life
10.
An. Facultad Med. (Univ. Repúb. Urug., En línea) ; 9(1): e205, jun. 2022. ilus, tab, graf
Article in Spanish | LILACS, UY-BNMED, BNUY | ID: biblio-1383561

ABSTRACT

Introducción: En Uruguay el cáncer de mama (CM) ocupa el primer lugar en incidencia y mortalidad por cáncer en mujeres. Objetivo: Evaluar el conocimiento de mujeres uruguayas sobre el tamizaje de cáncer de mama. Material y métodos: Se trata de un estudio observacional descriptivo y transversal. Se aplicó una encuesta dirigida a mujeres, que fue difundida mediante las redes sociales. El consentimiento informado se solicitó al inicio de la encuesta, como requisito excluyente para poder realizar la misma. Se mantuvo el anonimato de las pacientes en el análisis estadístico y se contó con la aprobación del Comité de Ética del Hospital de Clínicas. Resultados: Participaron 1859 mujeres. El 75.1% (1396) de las encuestadas reconoce el CM como el de mayor mortalidad en mujeres. El 52% (967) cree que 3 de cada 10 mujeres tienen riesgo de desarrollar CM, y 18.4% (342) desconoce su prevalencia. El 60.2% (1119) reconoce a la mamografía como prueba que ha logrado disminuir la mortalidad por CM. El 64.2% (1193) cree que se realiza a partir de los 40 años. Sobre la frecuencia, el 60.5% (1125) considera que se realiza de forma anual. Los factores de riesgo para desarrollar CM mayormente considerados fueron tabaquismo (60.9%, 1132), obesidad (57.%, 1060) y sedentarismo (56.8%,1056). Conclusiones: Nuestros resultados evidencian que las encuestadas están informadas de manera adecuada sobre la importancia del CM y de realizar el tamizaje mamográfico para prevenirlo; sin embargo, el 74.3% (1381) cree que el mismo, debe comenzar a hacerse a los 40 años.


Introduction: In Uruguay, breast cancer (BC) has the highest incidence and mortality of all cancer in women. Objectives : To assess the knowledge of Uruguayan women about breast cancer screening for the early detection of BC. Material and Methods : This is a descriptive and observational study. A survey was applied to woman, it was disseminated through social networks. Informed consent was requested at the beginning of the survey as an exclusive requirement to be able to carry it out. In the statistical analysis, the anonymity of the patients was maintained and the approval of the Ethics Committee of the Hospital de Clínicas was obtained. Results : 1859 women participated. 75.1% (1396) of those surveyed recognize BC as the one with the highest mortality in women. 52% (967) believe that 3 out of 10 women are at risk of developing BC, and 18.4% (342) do not know its prevalence. 60.2% (1119) recognize mammography as a test that has managed to reduce mortality from BC. 64.2% (1193) believe that it is done after 40 years of age. Regarding the frequency, 60.5% (1125) consider that it is carried out annually. The most considered risk factors for developing BC were smoking (60.9%, 1132), obesity (57%, 1.060) and sedentary lifestyle (56.8%, 1056). Conclusions : Our results show that the respondents are adequately informed about the importance of CM and the performance of screening mammography.


Introdução : No Uruguai, o câncer de mama (CM) tem a maior incidência e mortalidade de todos os cânceres em mulheres. Objetivos: Avaliar o conhecimento de mulheres uruguaias sobre o rastreamento do câncer de mama para a detecção precoce do CM. Material e Métodos : Trata-se de um estudo descritivo e observacional. Foi aplicado um questionário às mulheres, divulgado através das redes sociais. O consentimento informado foi solicitado no início da pesquisa como requisito exclusivo para poder realizá-la. Na análise estatística, foi mantido o anonimato dos pacientes e obtida a aprovação do Comitê de Ética do Hospital de Clínicas. Resultados: participaram 1859 mulheres. 75.1% (1396) dos pesquisados ​​reconhecem o CB como o de maior mortalidade em mulheres. 52% (967) acreditam que 3 em cada 10 mulheres estão em risco de desenvolver CM e 18.4% (342) não conhecem sua prevalência. 60.2% (1119) reconhecem a mamografia como um exame que tem conseguido reduzir a mortalidade por CM. 64.2% (1.193) acreditam que é feito após os 40 anos. Em relação à frequência, 60.5% (1125) consideram que é realizado anualmente. Os fatores de risco mais considerados para desenvolver CM foram tabagismo (60.9%, 1132), obesidade (57%, 1.060) e sedentarismo (56.8%, 1056). Conclusões: Nossos resultados mostram que as entrevistadas estão adequadamente informadas sobre a importância do MC e a realização da mamografia de rastreamento.


Subject(s)
Humans , Female , Adolescent , Adult , Middle Aged , Aged , Aged, 80 and over , Young Adult , Breast Neoplasms/prevention & control , Health Knowledge, Attitudes, Practice , Uruguay , Mammography/statistics & numerical data , Cross-Sectional Studies , Risk Factors , Health Surveys , Ultrasonography, Mammary/statistics & numerical data , Breast Self-Examination/statistics & numerical data , Educational Status , Information Seeking Behavior , Octogenarians
11.
Vaccine ; 40(15): 2311-2323, 2022 04 01.
Article in English | MEDLINE | ID: mdl-35279330

ABSTRACT

The new generation of vaccines for Chagas disease, are focused to induce both humoral and cellular response to effectively control Trypanosoma cruzi parasites. The administration of vaccine formulations intranasally has the advantage over parenteral routes that can induce a specific response at mucosal and systemic levels. This study aimed to evaluate and compare the immunogenicity and prophylactic effectiveness of two Trans-sialidase (TS)-based mucosal vaccines against T. cruzi administered intranasally. Vaccines consisted of a recombinant fragment of TS expressed in Lactococcus lactis formulated in two different adjuvants. The first, was an immunostimulant particle (ISPA, an ISCOMATRIX-like adjuvant), while the second was the dinucleotide c-di-AMP, which have shown immunostimulant properties at the mucosal level. BALB/c mice were immunized intranasally (3 doses, one every two weeks) with each formulation (TS + ISPA or TS + c-di-AMP) and with TS alone or vehicle (saline solution) as controls. Fifteen days after the last immunization, both TS + ISPA or TS + c-di-AMP induced an evident systemic humoral and cellular response, as judged by the increased plasma anti-TS IgG2a titers and IgG2a/IgG1 ratio and enhanced cellular response against TS. Plasma derived antibodies from TS + c-di-AMP also inhibit in vitro the invasion capacity of T. cruzi. Furthermore, specific secretory IgA was more enhanced in TS + c-di-AMP group. Protective efficacy was proved in vaccinated animals by an oral T. cruzi-challenge. Parasitemia control was only achieved by animals vaccinated with TS + c-di-AMP, despite all vaccinates groups showed enhanced CD8+IFN-γ+ T cell numbers. In addition, it was reflected during the acute phase in a significant reduction of tissue parasite load, clinical manifestations and diminished tissue damage. The better prophylactic capacity elicited by TS + c-di-AMP was related to the induction of neutralizing plasma antibodies and augmented levels of mucosal IgA since TS + ISPA and TS + c-di-AMP groups displayed similar immunogenicity and CD8+IFN-γ+ T-cell response. Therefore, TS + c-di-AMP formulation appears as a promising strategy for prophylaxis against T. cruzi.


Subject(s)
Chagas Disease , Protozoan Vaccines , Trypanosoma cruzi , Animals , Chagas Disease/prevention & control , Dinucleoside Phosphates , Glycoproteins , Immunization , Mice , Mice, Inbred BALB C , Neuraminidase
12.
Front Cell Infect Microbiol ; 11: 713150, 2021.
Article in English | MEDLINE | ID: mdl-34796122

ABSTRACT

Trypanosoma cruzi infection in humans leads to progression to chronic chagasic myocarditis (CCM) in 30% of infected individuals, paralleling T cell inflammatory infiltrates in the heart tissue. T-cell trafficking into the hearts of CCM patients may be modulated by in situ expression of chemotactic or haptotactic molecules, as the chemokine CXCL12, the cytokine tumor necrosis factor-alpha (TNF-α), and extracellular matrix proteins (ECM), such as fibronectin. Herein we evaluated the expression of fibronectin, CXCL12, and TNF-α in the myocardial tissue of T. cruzi seropositive (asymptomatic or with CCM), as well as seronegative individuals as healthy controls. Hearts from CCM patients exhibited enhanced expression of these three molecules. CXCL12 and TNF-α serum levels were also increased in CCM individuals. We then evaluated T lymphocytes from chronic chagasic patients by cytofluorometry, in terms of membrane expression levels of molecules involved in cell activation and cell migration, respectively, HLA-DR and the VLA-4 (very late antigen-4, being one integrin-type fibronectin receptor). Indeed, the expression of HLA-DR and VLA-4 was enhanced on T lymphocytes from chagasic patients, especially in the CCM group. To further approach the dynamics of T cell migratory events, we performed fibronectin-, TNF-α-, and CXCL12-driven migration. Peripheral blood mononuclear cells (PBMCs) and T cells from CCM patients presented an ex vivo enhanced migratory capacity driven by fibronectin alone when this ECM protein was placed in the membrane of transwell migration chambers. When TNF-α was previously placed upon fibronectin, we observed a further and significant increase in the migratory response of both PBMCs and T lymphocytes. Overall, these data suggest the existence in patients with chronic Chagas disease of a cardiac inflammatory infiltrate vector that promotes the recruitment and accumulation of activated T cells, driven in part by enhanced tissue expression of fibronectin and TNF-α, as well as the respective corresponding VLA-4 and TNF receptors.


Subject(s)
Chagas Disease , Integrin alpha4beta1 , Tumor Necrosis Factor-alpha/genetics , Humans , Leukocytes, Mononuclear , T-Lymphocytes
13.
J Phys Chem B ; 125(4): 1241-1247, 2021 02 04.
Article in English | MEDLINE | ID: mdl-33474933

ABSTRACT

Droplet evaporation on surfaces is ubiquitous and affects areas as diverse as climate, microbiology, the chemical industry, and materials science. While solute concentration is the universally taken-for-granted behavior in drop evaporation, the present work shows that saline droplets evaporating on nanoporous thin-film surfaces can get diluted rather than concentrated. The driving mechanism of this phenomenon is attributed to the flow drawn from the drop through the nanopores by an annular peripheral evaporation. This fluid transport can continuously collect the salt solution from a concentrated region of the droplet, which is induced by radial microflows during drop evaporation. The coupling of these processes leads to the overall drop dilution effect. The influence of substrate temperature and drop volume was also investigated. This study opens up new perspectives on many natural phenomena and offers alternatives for physicochemical applications in small dimensions as well as for water desalination technologies.

14.
Clin Rheumatol ; 40(7): 2955-2963, 2021 Jul.
Article in English | MEDLINE | ID: mdl-33438080

ABSTRACT

Evidence for Chagas disease reactivation (CDR) in rheumatologic patients under rheumatologic treatments (RTs) is scarce. To screen and follow-up patients with rheumatic diseases and concomitant Chagas disease under RT to detect CDR and to describe a possible relationship between CDR and specific RT. An observational, longitudinal, prospective, consecutive study was carried out between 2018 and 2020. Included patients were evaluated during the follow-up for clinical and laboratorial manifestations of CDR. Direct blood parasitological examination (Strout method) and polymerase chain reaction (PCR) were employed to diagnose CDR. The dynamic of anti-T. cruzi-specific antibodies was also assessed by IHA and ELISA (total IgG and Anti-SAPA). Fifty-one patients were included (86% women). Rheumatoid arthritis was the predominant disease (57%). Classic DMARDs (86.3%) and corticosteroids (61%) were the most frequent RT. CDR was developed in 6 patients (11.7%), exhibiting both positive Strout and PCR. Symptomatic reactivation of CD (fever, asthenia, arthralgias, myalgias) occurred in two patients who had previously been diagnosed with it. Regardless of the different RT, all patients who experienced CDR had previously received more than ≥ 20 mg/day of prednisone equivalent. Despite immunosuppression, patients with CDR exhibited increased levels of specific anti-T. cruzi and anti-SAPA antibodies, which decreased after anti-parasitic treatment. CDR is possible in rheumatologic patients, especially after receiving high doses of corticosteroids. Since CDR symptoms may mimic rheumatic disease activity, monitoring of Chagas disease is highly recommended before, during and after immunosuppression. Key Points • Chagas disease reactivation (CDR) in the context of rheumatological treatment was associated to high doses of corticosteroids. • CDR was associated with an increase in anti-T. cruzi antibodies despite the immunosuppressive treatment. • Suspecting and anticipating CDR is mandatory in this patient population to diagnose and treat it.


Subject(s)
Arthritis, Rheumatoid , Chagas Disease , Trypanosoma cruzi , Arthritis, Rheumatoid/complications , Arthritis, Rheumatoid/drug therapy , Chagas Disease/complications , Chagas Disease/drug therapy , Female , Humans , Immunosuppression Therapy , Male , Prospective Studies
15.
Pathogens ; 9(11)2020 Nov 12.
Article in English | MEDLINE | ID: mdl-33198223

ABSTRACT

A central aspect of Brucella pathogenicity is its ability to invade, survive, and replicate in diverse phagocytic and non-phagocytic cell types, leading to chronic infections and chronic inflammatory phenomena. Adhesion to the target cell is a critical first step in the invasion process. Several Brucella adhesins have been shown to mediate adhesion to cells, extracellular matrix components (ECM), or both. These include the sialic acid-binding proteins SP29 and SP41 (binding to erythrocytes and epithelial cells, respectively), the BigA and BigB proteins that contain an Ig-like domain (binding to cell adhesion molecules in epithelial cells), the monomeric autotransporters BmaA, BmaB, and BmaC (binding to ECM components, epithelial cells, osteoblasts, synoviocytes, and trophoblasts), the trimeric autotransporters BtaE and BtaF (binding to ECM components and epithelial cells) and Bp26 (binding to ECM components). An in vivo role has also been shown for the trimeric autotransporters, as deletion mutants display decreased colonization after oral and/or respiratory infection in mice, and it has also been suggested for BigA and BigB. Several adhesins have shown unipolar localization, suggesting that Brucella would express an adhesive pole. Adhesin-based vaccines may be useful to prevent brucellosis, as intranasal immunization in mice with BtaF conferred high levels of protection against oral challenge with B. suis.

16.
Free Radic Biol Med ; 156: 137-143, 2020 08 20.
Article in English | MEDLINE | ID: mdl-32574682

ABSTRACT

We previously demonstrated that oral supplementation with antioxidants induced hyperactivity of hypothalamus-pituitary-adrenal (HPA) axis, attested by hypercorticoidism, through an up-regulation of adrenocorticotrophic hormone (ACTH) receptors (MC2R) in adrenal. This study analyzed the role of peroxisome proliferator-activated receptor (PPAR)-γ on HPA axis hyperactivity induced by N-acetyl-cysteine (NAC). Male Swiss-Webster mice were orally treated with NAC for 1, 3, 5, 10, 15, or 18 consecutive days. The PPAR-γ agonist rosiglitazone and/or antagonist GW9662 were daily-injected i.p. for 5 consecutive days, starting concomitantly with NAC treatment. Rosiglitazone treatment inhibited NAC-induced adrenal hypertrophy and hypercorticoidism. Rosiglitazone also significantly reversed the NAC-induced increase in the MC2R expression in adrenal, but not steroidogenic acute regulatory protein (StAR). NAC treatment reduces the expression of PPARγ in the adrenals, but rosiglitazone did not restore the expression of this cytoprotective gene. In addition, GW9662 blocked the ability of rosiglitazone to decrease plasma corticosterone levels in NAC-treated mice. In conclusion, our findings showed that antioxidant supplementation induced a state of hypercorticoidism through down-regulation of PPARγ expression in the adrenals, in a mechanism probably related to a down-regulation of ACTH receptor expression.


Subject(s)
PPAR gamma , Thiazolidinediones , Acetylcysteine/pharmacology , Adrenal Glands/metabolism , Animals , Hypothalamo-Hypophyseal System/metabolism , Male , Mice , PPAR gamma/genetics , PPAR gamma/metabolism , Pituitary-Adrenal System/metabolism , Receptors, Corticotropin , Thiazolidinediones/pharmacology
17.
Microbes Infect ; 22(9): 407-415, 2020 10.
Article in English | MEDLINE | ID: mdl-32535086

ABSTRACT

Brucella infection is frequently acquired through the respiratory route. The pathogen disseminates systemically from the lungs to infect peripheral organs. In this review we summarize the existing data on the pathogenesis of inhalational Brucella infection, the pulmonary immune response to the pathogen, and potential strategies for inducing protective lung immunity.


Subject(s)
Brucellosis/immunology , Immunity , Lung/immunology , Animals , Brucella/immunology , Brucella/pathogenicity , Brucella Vaccine/immunology , Humans , Vaccination , Virulence/immunology
18.
J Health Care Poor Underserved ; 31(1): 35-42, 2020.
Article in English | MEDLINE | ID: mdl-32037315

ABSTRACT

Use of community-based participatory research (CBPR) principles can help identify strategies for development and implementation of studies that can address oral health disparities disfavoring African American youth. This paper summarizes approaches of the Howard Meharry Adolescent Caries Study (HMACS) to provide sustained oral health services beyond the life of a research study.


Subject(s)
Black or African American , Community-Based Participatory Research/organization & administration , Dental Caries/ethnology , Oral Health , School Health Services/organization & administration , Adolescent , Dental Caries/etiology , Health Promotion , Healthcare Disparities/ethnology , Humans , Pediatric Dentistry , United States
19.
Biochim Biophys Acta Mol Basis Dis ; 1866(3): 165642, 2020 03 01.
Article in English | MEDLINE | ID: mdl-31866417

ABSTRACT

Studies in mice undergoing acute Trypanosoma cruzi infection and patients with Chagas disease, led to identify several immune-neuroendocrine disturbances and metabolic disorders. Here, we review relevant findings concerning such abnormalities and discuss their possible influence on disease physiopathology.


Subject(s)
Chagas Disease/immunology , Metabolic Diseases/immunology , Neuroendocrine Cells/immunology , Trypanosoma cruzi/immunology , Animals , Chagas Disease/parasitology , Humans , Metabolic Diseases/parasitology , Neuroendocrine Cells/parasitology
20.
Front Immunol ; 10: 1775, 2019.
Article in English | MEDLINE | ID: mdl-31402921

ABSTRACT

Brucella enters their hosts mostly through mucosae from where it spreads systemically. Adhesion to extracellular matrix (ECM) components or to host cells is important for the infectious process, and is mediated by several adhesins, including the BtaF trimeric autotransporter. Although Th1 responses and gamma interferon (IFN-γ) are important for protection, antibodies able to block adhesions might also contribute to prevent Brucella infection. We evaluated the importance of BtaF for respiratory Brucella infection, and characterized the immune response and protection from mucosal challenge induced by nasal vaccination with recombinant BtaF. While lung CFU numbers did not differ at day 1 p.i. between mice intratracheally inoculated with B. suis M1330 (wild type) and those receiving a ΔbtaF mutant, they were reduced in the latter group at 7 and 30 days p.i. For vaccination studies the BtaF passenger domain was engineered and expressed as a soluble trimeric protein. Mice were immunized by the nasal route with BtaF or saline (control group) plus the mucosal adjuvant c-di-AMP. Specific anti-BtaF antibodies (IgG and IgA) were increased in serum, including a mixed IgG2a/IgG1 response. In vitro, these antibodies reduced bacterial adhesion to A549 alveolar epithelial cells. Specific IgA antibodies were also increased in several mucosae. Spleen cells from BtaF immunized mice significantly increased their IL-2, IL-5, IL-17, and IFN-γ secretion upon antigen stimulation. In cervical draining lymph nodes, antigen-experienced CD4+ T cells were maintained mainly as central memory cells. A BtaF-specific delayed-type hypersensitivity response was detected in BtaF immunized mice. Lung cells from the latter produced high levels of IFN-γ upon antigen stimulation. Although nasal immunization with BtaF did not protect mice against B. suis respiratory challenge, it conferred significant protection from intragastric challenge; the splenic load of B. suis was reduced by 3.28 log CFU in immunized mice. This study shows that nasal vaccination with BtaF+c-di-AMP protects against intragastric challenge with B. suis by inducing local and systemic antibody responses, central memory CD4+ T cells and strong Th1 responses. Therefore, although BtaF vaccination did not protect from B. suis respiratory infection, this adhesin constitutes a promising immunogen against mucosal B. suis infection.


Subject(s)
Adhesins, Bacterial/genetics , Antigens, Bacterial/immunology , Brucella suis/physiology , Brucellosis/immunology , Brucellosis/microbiology , Adaptive Immunity , Adhesins, Bacterial/metabolism , Administration, Intranasal , Animals , CD4-Positive T-Lymphocytes , Dinucleoside Phosphates/metabolism , Female , Humans , Immunity, Mucosal/immunology , Immunization/methods , Mice , Virulence
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