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1.
Lancet Reg Health Am ; 29: 100647, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38187006

RESUMO

Background: Human Bocaviruses (HBoV) can cause acute respiratory tract infections. High coinfection rates cloud its pathogenicity. This study sought to describe the clinical features of HBoV1 disease in children and adults with Influenza-like illness (ILI), exploring associations between viral load, clinical features, and seasonality. Methods: Patients who tested positive for HBoV1 by polymerase chain reaction, enrolled from April 2010 to March 2014 in the ILI002 prospective observational cohort study were included in this cross-sectional nested study. Participants were included in ILI002 if they presented with signs and/or symptoms suggestive of influenza-like illness. Samples were tested for viral load, and NP1 and VP1/VP2 phylogenetic analyses, except for the samples lacking suitable and viable clinical material for genotyping. Findings: We identified HBoV1 in 157 (2.8%) of participants. Prevalence was 4.5% in children and 1.8% in adults. Single HBoV1 detection occurred in 41.1% and 46.3% of children and adults, respectively. Children commonly experienced fever (83.3%), cough with sputum (74.4%), and shortness of breath (72.2%). In the multivariate analysis of children, significant positive associations were detected between viral loads and age (0.20 [95% CI: 0.07, 0.33]), and the presence of fever (2.64 [95% CI: 1.35, 3.94]), nasal congestion (1.03 [95% CI: 0.07, 1.99]), dry cough (1.32 [95% CI: 0.42, 2.22]), chest congestion (1.57 [95% CI: 0.33, 2.80]), red eyes (1.25 [95% CI: 0.35, 2.14]), cough with sputum (1.79 [95% CI: 0.80, 2.78]), and other signs and symptoms such as chills, dizziness, and diaphoresis (1.73 [95% CI: 0.19, 3.27]). In contrast, significant negative associations were found between viral loads and percent neutrophils on the blood count (-0.04 [95% CI: -0.06, -0.02]), fatigue (-1.60 [95% CI: -2.46, -0.74]) and the presence of other symptoms or signs, including adenopathy and rash (-1.26 [95% CI: -2.31, -0.21]). Adults commonly experienced sore throat (73.1%), fatigue (77.4%), and headache (73.1%). In the multivariate analysis of adults, significant positive associations were detected between viral load and body mass index (0.13 [95% CI: 0.04, 0.21]), and the presence of confusion (1.54 [95% CI: 0.55, 2.53]), and sore throat (1.03 [95% CI: 0.20, 1.85]), and significant negative associations were detected between viral load and chest congestion (-1.16 [95% CI: -2.07, -0.24]). HBoV1 was detected throughout the year irrespective of season, temperature, and humidity. Interpretation: This study demonstrated the importance of detecting HBoV1 in patients with influenza-like illness either as single infection or co-infection, in both adults and children, and improves the characterization of HBoV1 seasonality, clinical features, and viral load. Phylogenetic analyses show a high conservation. Funding: The Mexican Emerging Infectious Diseases Clinical Research Network (LaRed), CONACYT (Fondo Sectorial SSA/IMSS/ISSSTE, Projects No. 71260 and No. 127088), Fondos federales no. HIM/2015/006, NIAID, NIH through a contract with Westat, Inc. (HHSN2722009000031, HHSN27200002), NCI, NIH (75N91019D00024, 75N91019F00130). Additional information at the end of the manuscript.

2.
Clin Exp Allergy ; 53(8): 821-832, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-36779555

RESUMO

BACKGROUND: Allergen-specific immunotherapy (AIT) is the only disease-modifying treatment approach to change disease-causing allergens. Hypoallergenic derivatives show promise as potential therapeutics, amongst which BTH2 was designed to induce tolerance against Blomia tropicalis allergy. Our aim was to investigate the hypoallergenicity and immunoregulatory activity of BTH2 in vitro and its therapeutic potential in a mouse model of AIT. METHODS: Recombinant Blo t 5 and Blo t 21 allergens and their hybrid derivatives (BTH1 and BTH2) were expressed and purified. IgE binding capacity was tested by ELISA using sera from Brazilian, Colombian, and Ecuadorian subjects. Secretion of cytokines in supernatants from human cell cultures was measured following stimulation with the four recombinants and controls. The capacity of BTH2 to ameliorate allergic airway inflammation induced by B. tropicalis extract was evaluated in a murine model of AIT. RESULTS: rBlo t 5 and rBlo t 21 were identified as major allergens in Latin American patients, and BTH2 had the lowest IgE binding. In vitro stimulation of human cells induced greater levels of IL-10 and IFN-γ and reduced the secretion of Th2 cytokines. BTH2 ameliorated allergic airway inflammation in B. tropicalis-challenged A/J mice, as evidenced by the histopathological and humoral biomarkers: decreased Th2 cytokines and cellular infiltration (especially eosinophils), lower activity of eosinophil peroxidase, an increase in IgG blocking antibodies and strong reduction of mucus production by goblet cells. CONCLUSIONS: Our study shows that BTH2 represents a promising candidate for the treatment of B. tropicalis allergy with hypoallergenic, immune regulatory and therapeutic properties. Further pre-clinical studies are required in murine models of chronic asthma to further address the efficacy and safety of BTH2 as a vaccine against B. tropicalis-induced allergy.


Assuntos
Hipersensibilidade , Humanos , Camundongos , Animais , Modelos Animais de Doenças , Hipersensibilidade/terapia , Alérgenos , Inflamação , Citocinas , Dessensibilização Imunológica , Imunoglobulina E
3.
Protein Expr Purif ; 199: 106150, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35944614

RESUMO

Common strategies to improve recombinant protein production in Escherichia coli often involve the test and optimization of several different variables, when using traditional expression vectors that are commercially available. Now, modern synthetic biology-based strategies allow for extensive modifications of these traditional vectors, or even construction of entirely new modular vectors, so as to permit tunable production of the recombinant proteins of interest. Herein, we describe the engineering of a new expression operating unit (EOU; 938 bp) for producing recombinant proteins in E. coli, through the combinatorial assembly of standardized and well-characterized genetic elements required for transcription and translation (promoter, operator site, RBS, junction RBS-CDS, cloning module, transcriptional terminator). We also constructed a novel T7 promoter variant with increased transcriptional activity (1.7-fold higher), when compared to the canonical wild type T7 promoter sequence. This new EOU yielded an improved production of the reporter protein superfolder GFP (sfGFP) in E. coli BL21(DE3) (relative fluorescence units/RFU = 70.62 ± 1.62 A U.) when compared to a high-producing control expression vector (plasmid BBa_I746909; RFU = 59.68 ± 1.82 A U.). The yields of purified soluble recombinant sfGFP were also higher when using the new EOU (188 mg L-1 culture vs. 108 mg L-1 in the control) and it performed similarly well when inserted into different plasmid backbones (pOPT1.0/AmpR and pOPT2.0/CmR).


Assuntos
Escherichia coli , Vetores Genéticos , Escherichia coli/genética , Escherichia coli/metabolismo , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Plasmídeos/genética , Regiões Promotoras Genéticas , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo
4.
Transbound Emerg Dis ; 69(5): e2994-e3006, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35801561

RESUMO

Toxocariasis is an infection caused by the round worms Toxocara canis and Toxocara cati. It occurs worldwide though it is more prevalent in developing countries. For the diagnosis of toxocariasis, the most used method is the indirect enzyme-linked immunosorbent assay (indirect ELISA), based on the detection of specific antibodies using the excreted/secreted products from T. canis larvae (TES) as antigens, but it cross-reacts with several helminth infections. For this reason, there is a need to investigate species-specific immunoreactive proteins, which can be used for the development of a more sensitive and specific diagnosis. This study aims to investigate immunoreactive protein candidates to be used for the development of a more sensitive and specific diagnosis of Toxocara spp. infection in humans. We have used immunoblotting and mass spectrometry to select four Toxocara canis immunoreactive proteins that were recombinantly expressed in bacteria and evaluated as potential new diagnostic antigens (rMUC3, rTES 26, rTES32 and rCTL4). The recognition of these recombinant proteins by total serum IgG and IgG4 was assayed using the purified proteins in an isolated manner or in combination. The IgG ELISAs performed with individual recombinant antigens reached values of sensitivity and specificity that ranged from 91.7% to 97.3% and 94.0% to 97.9%, respectively. Among the analyses, the IgG4 immunoassay was proven to be more effective, revealing a sensitivity that ranged from 88.8% to 98.3% and a specificity of 97.8%-97.9%. The IgG4 ELISA was shown to be more effective and presented no cross-reactivity when using combinations of the rTES 26 and rCTL4 recombinant proteins. The combination of these two molecules achieved 100% sensitivity and specificity. The use of only two recombinant proteins can contribute to improve the current panorama of toxocariasis immunodiagnosis for, with a better optimization and reduced cost.


Assuntos
Toxocara canis , Toxocaríase , Animais , Antígenos de Helmintos , Ensaio de Imunoadsorção Enzimática/métodos , Ensaio de Imunoadsorção Enzimática/veterinária , Humanos , Immunoblotting/veterinária , Imunoglobulina G , Testes Imunológicos/veterinária , Proteômica , Proteínas Recombinantes , Toxocara , Toxocaríase/diagnóstico
5.
Exp Appl Acarol ; 86(3): 385-406, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35286553

RESUMO

Blomia tropicalis and Dermatophagoides pteronyssinus play an important role in triggering allergy. Glycycometus malaysiensis causes IgE reaction in sensitive people, but is rarely reported in domestic dust, because it is morphologically similar to B. tropicalis making the identification of these species difficult. The identification of mites is mostly based on morphology, a time-consuming and ambiguous approach. Herein, we describe a multiplex polymerase chain reaction (mPCR) assay based on ribosomal DNA capable to identify mixed cultures of B. tropicalis, D. pteronyssinus and G. malaysiensis, and/or to identify these species from environmental dust. For this, the internal transcribed spacer 2 (ITS2) regions, flanked by partial sequences of the 5.8S and 28S genes, were PCR-amplified, cloned and sequenced. The sequences obtained were aligned with co-specific sequences available in the GenBank database for primer design and phylogenetic studies. Three pairs of primers were chosen to compose the mPCR assay, which was used to verify the frequency of different mites in house dust samples (n = 20) from homes of Salvador, Brazil. Blomia tropicalis was the most frequent, found in 95% of the samples, followed by G. malaysiensis (70%) and D. pteronyssinus (60%). Besides reporting for the first time the occurrence of G. malaysiensis in Brazil, our results confirm the good resolution of the ITS2 region for mite identification. Furthermore, the mPCR assay proved to be a fast and reliable tool for identifying these mites in mixed cultures and could be applied in future epidemiological studies, and for quality control of mite extract production for general use.


Assuntos
Dermatophagoides pteronyssinus , Ácaros , Animais , Antígenos de Dermatophagoides , Brasil , Poeira , Humanos , Reação em Cadeia da Polimerase Multiplex , Filogenia
6.
Vaccine ; 40(6): 912-923, 2022 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-35012775

RESUMO

Toxocariasis is a neglected parasitic zoonosis of global importance. The development of a formulation that can be used as a vaccine would help the definitive control of the infection. Preclinical studies selected two recombinant T. canis proteins (rTcVcan and rTcCad) which significantly protected mice against larval migration. In the present work, these proteins plus three adjuvants (Alhydrogel®, PAM3CSK4®, and Quil-A®) were used to immunize mice against toxocariasis; blood samples were collected three times to measure IgG (total, IgG1, IgG2a), IgA, and IgE via indirect ELISA. Cytokines (IL-5, TNF-α, and IL-10) were measured in splenocytes supernatant, and T. canis larvae were quantified in tissues. The best protein + adjuvant pair found (rTVcan + QuialA®) was then used to immunize T. canis-free puppies (n = 18) that were experimentally infected with T. canis and T. canis naturally-infected puppies (n = 6). Immunoglobulin (IgA, IgE, IgG, IgG1, and IgG2a), parasite load (eggs in feces), number of expelled adults and eggs extracted from the female uterus, and their fertility percentages were analyzed. In mice, it was observed a highly significant reduction (73%) of tissue larvae, a mixed cytokine profile (Th1/Th2), and anti-T. canis antibody titers (IgG, IgG1, IgG2a) using rTVcan + QuialA® mix. In canines, rTVcan + QuialA® promoted reduction in the parasite eggs in feces (95%) and eggs reduction obtained from the uteri of pharmacologically expelled adult females (58.38%). In our knowledge this is the first canine clinical trial of a vaccine with T. canis recombinant proteins. The formulation used has been shown to efficiently stimulate the production of antibodies against infection by T. canis. In the canine, a significant reduction in the number of eggs expelled by the experimental animals that received the formulation prophylactically was evidenced. Future tests should be developed to evaluate the duration of the protective effect and analyze other immune pathways that could be stimulated by the formulation used.


Assuntos
Toxocara canis , Toxocaríase , Animais , Modelos Animais de Doenças , Cães , Feminino , Imunização , Imunoglobulina G , Camundongos , Proteínas Recombinantes , Toxocaríase/parasitologia , Toxocaríase/prevenção & controle
7.
F1000Res ; 11: 1184, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-37965037

RESUMO

Background: Since the beginning of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak, different animal species have been implicated as possible intermediate hosts that could facilitate the transmission of the virus between species. The detection of these hosts has intensified, reporting wild, zoo, farm, and pet animals. The goal of this study was to determine the seroprevalence of anti-SARS-CoV-2 immunoglobulins (IgG) in domestic dogs and cats and its epidemiological association with the frequency of coronavirus disease 2019 (COVID-19) patients in Villavicencio, Colombia. Methods: 300 dogs and 135 cats were randomly selected in a two-stage distribution by clusters according to COVID-19 cases (positive RT-qPCR for SARS-CoV-2) within the human population distributed within the eight communes of Villavicencio. Indirect enzyme-linked immunosorbent assay (ELISA) technique was applied in order to determine anti-SARS-CoV-2 IgG in sera samples. Kernel density estimation was used to compare the prevalence of COVID-19 cases with the seropositivity of dogs and cats. Results: The overall seroprevalence of anti-SARS-CoV-2 IgG was 4.6% (95% CI=3.2-7.4). In canines, 3.67% (95% CI=2.1-6.4) and felines 6.67% (95% CI=3.6-12.18). Kernel density estimation indicated that seropositive cases were concentrated in the southwest region of the city. There was a positive association between SARS-CoV-2 seropositivity in pet animals and their habitat in Commune 2 (adjusted OR=5.84; 95% CI=1.1-30.88). Spearman's correlation coefficients were weakly positive ( p=0.32) between the ratio of COVID-19 cases in November 2020 and the results for domestic dogs and cats from the eight communes of Villavicencio. Conclusions: In the present research cats were more susceptible to SARS-CoV-2 infection than dogs. This study provides the first positive results of anti-SARS-CoV-2 ELISA serological tests in domestic dogs and cats in Colombia with information about the virus transmission dynamics in Latin America during the COVID-19 pandemic.


Assuntos
COVID-19 , Doenças do Gato , Doenças do Cão , Humanos , Gatos , Cães , Animais , SARS-CoV-2 , COVID-19/epidemiologia , COVID-19/veterinária , Colômbia/epidemiologia , Pandemias , Estudos Soroepidemiológicos , Doenças do Cão/epidemiologia , Anticorpos Antivirais , Imunoglobulina G
8.
Parasit Vectors ; 14(1): 95, 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33546758

RESUMO

BACKGROUND: Although Toxocara spp. infection has a worldwide distribution, to our knowledge, no data from birth cohorts have been reported in published studies on the potential for congenital transmission and determinants of infection in early childhood. METHODS: We followed 290 mother-infant pairs from birth to 5 years of age through periodic collection of data and samples at birth, 7 and 13 months and 2, 3 and 5 years of age. Data on potential risk factors and confounders were collected by maternal questionnaire. Blood for plasma was collected from the mother at time of birth and periodically from the child for detection of anti-Toxocara spp. immunoglobulin G (IgG) antibodies using a Toxocara canis larval excretory-secretory antigen-based enzyme-linked immunosorbent assay. Stool samples were collected from the mother around the time of birth and periodically from the child for microscopic detection of soil-transmitted helminths (STH). Associations between potential risk factors and Toxocara spp. seroprevalence and seroconversion were estimated using multivariable logistic regression and generalized estimating equations. RESULTS: Toxocara spp. seroprevalence was 80.7% in mothers and in children was 0%, 9.3%, 48.4%, 64.9%, and 80.9% at 7 months, 13 months, 2, 3 and 5 years, respectively. Risk factors significantly associated with increases in seroprevalence over the first 5 years of life in multivariable analyses were age [Odds ratio (OR) 2.06, 95% confidence interval (CI) 1.39-2.27, P < 0001], male sex (female vs. male: OR 0.66, 95% CI 0.48-0.89, P = 0.006), maternal ethnicity (non-Afro vs. Afro-Ecuadorian: OR 0.65, 95% CI 0.47-0.91, P = 0.011), lower maternal educational and socioeconomic level, and childhood STH (OR 2.29, 95% CI 1.51-3.47, P < 0.001). Seroconversion rates for infection were greatest at 2 years of age (3.8%/month). Factors associated significantly with seroconversion at 2, 3 or 5 years were childhood STH infection, male sex, and more frequent domestic cat exposure. CONCLUSIONS: Our data, from an area of high Toxocara spp. endemicity, indicate no congenital transmission but high rates of seroconversion after 13 months of age reaching maternal levels of seroprevalence by 5 years of age. Factors associated with seroprevalence and seroconversion included STH infections, domestic cats, maternal ethnicity, male sex, STH infections, and markers of greater poverty.


Assuntos
Anticorpos Anti-Helmínticos/sangue , Toxocara/imunologia , Toxocaríase/congênito , Toxocaríase/transmissão , Animais , Pré-Escolar , Equador/epidemiologia , Fezes/parasitologia , Feminino , Humanos , Imunoglobulina G/sangue , Lactente , Recém-Nascido , Masculino , Mães , Estudos Prospectivos , Fatores de Risco , Estudos Soroepidemiológicos , Inquéritos e Questionários , Toxocaríase/epidemiologia , Toxocaríase/imunologia
9.
Clin Gastroenterol Hepatol ; 19(6): 1189-1199.e30, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-32445952

RESUMO

BACKGROUND & AIMS: A high-fat diet has been associated with an increased risk of ulcerative colitis (UC). We studied the effects of a low-fat, high-fiber diet (LFD) vs an improved standard American diet (iSAD, included higher quantities of fruits, vegetables, and fiber than a typical SAD). We collected data on quality of life, markers of inflammation, and fecal markers of intestinal dysbiosis in patients with UC. METHODS: We analyzed data from a parallel-group, cross-over study of 17 patients with UC in remission or with mild disease (with a flare within the past 18 mo), from February 25, 2015, through September 11, 2018. Participants were assigned randomly to 2 groups and received a LFD (10% of calories from fat) or an iSAD (35%-40% of calories from fat) for the first 4-week period, followed by a 2-week washout period, and then switched to the other diet for 4 weeks. All diets were catered and delivered to patients' homes, and each participant served as her or his own control. Serum and stool samples were collected at baseline and week 4 of each diet and analyzed for markers of inflammation. We performed 16s ribosomal RNA sequencing and untargeted and targeted metabolomic analyses on stool samples. The primary outcome was quality of life, which was measured by the short inflammatory bowel disease (IBD) questionnaire at baseline and week 4 of the diets. Secondary outcomes included changes in the Short-Form 36 health survey, partial Mayo score, markers of inflammation, microbiome and metabolome analysis, and adherence to the diet. RESULTS: Participants' baseline diets were unhealthier than either study diet. All patients remained in remission throughout the study period. Compared with baseline, the iSAD and LFD each increased quality of life, based on the short IBD questionnaire and Short-Form 36 health survey scores (baseline short IBD questionnaire score, 4.98; iSAD, 5.55; LFD, 5.77; baseline vs iSAD, P = .02; baseline vs LFD, P = .001). Serum amyloid A decreased significantly from 7.99 mg/L at baseline to 4.50 mg/L after LFD (P = .02), but did not decrease significantly compared with iSAD (7.20 mg/L; iSAD vs LFD, P = .07). The serum level of C-reactive protein decreased numerically from 3.23 mg/L at baseline to 2.51 mg/L after LFD (P = .07). The relative abundance of Actinobacteria in fecal samples decreased from 13.69% at baseline to 7.82% after LFD (P = .017), whereas the relative abundance of Bacteroidetes increased from 14.6% at baseline to 24.02% on LFD (P = .015). The relative abundance of Faecalibacterium prausnitzii was higher after 4 weeks on the LFD (7.20%) compared with iSAD (5.37%; P = .04). Fecal levels of acetate (an anti-inflammatory metabolite) increased from a relative abundance of 40.37 at baseline to 42.52 on the iSAD and 53.98 on the LFD (baseline vs LFD, P = .05; iSAD vs LFD, P = .09). The fecal level of tryptophan decreased from a relative abundance of 1.33 at baseline to 1.08 on the iSAD (P = .43), but increased to a relative abundance of 2.27 on the LFD (baseline vs LFD, P = .04; iSAD vs LFD, P = .08); fecal levels of lauric acid decreased after LFD (baseline, 203.4; iSAD, 381.4; LFD, 29.91; baseline vs LFD, P = .04; iSAD vs LFD, P = .02). CONCLUSIONS: In a cross-over study of patients with UC in remission, we found that a catered LFD or iSAD were each well tolerated and increased quality of life. However, the LFD decreased markers of inflammation and reduced intestinal dysbiosis in fecal samples. Dietary interventions therefore might benefit patients with UC in remission. ClinicalTrials.gov no: NCT04147598.


Assuntos
Colite Ulcerativa , Qualidade de Vida , Estudos Cross-Over , Dieta , Disbiose , Fezes , Feminino , Humanos , Inflamação , Masculino
10.
Orinoquia ; 24(2): 79-95, July-Dec. 2020. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1250436

RESUMO

Abstract Based on prevalence and impact on public health, toxocariasis is an underestimated zoonosis in developing and developed countries. The transmission of Toxocara spp. involves pets, stray dogs and cats (Canis familiaris and Felis catus, respectively), which spread the parasite's eggs in their feces to the environment. One of the main risk factors for the infection and development of human toxocariasis, is to cohabit with puppies and kittens. For a long time, the preventive strategy for this parasitic infection has been the regular use of antiparasitic drugs to reduce parasite burden in the short term. A long lasting immunological protection can be achieved with vaccination, however, a vaccine is not yet available. Therefore, it is fundamental to know and to understand the state of the art of vaccine development for effective control of this zoonosis. This paper reviews the experimental studies focused on vaccine development for toxocariasis control, and special attention is given to relevant epidemiological studies on the importance of dogs in human toxocariasis.


Resumen Según la prevalencia y el impacto en la salud pública, la toxocariasis es una zoonosis subestimada en los países en desarrollo y desarrollados. La transmisión de Toxocara spp. involucra animales de compañía caninos y felinos, como también perros y gatos sin hogar (Canis familiaris y Felis catus, respectivamente), que diseminan los huevos del parásito en sus heces al medio ambiente. Uno de los principales factores de riesgo para la infección y el desarrollo de la toxocariasis humana es convivir con cachorros felinos y caninos. Durante mucho tiempo, la estrategia preventiva para esta infección parasitaria ha sido el uso regular de medicamentos antiparasitarios para reducir la carga parasitaria a corto plazo. Se puede lograr una protección inmunológica duradera con la vacunación, sin embargo, todavía no se dispone de una vacuna. Por lo tanto, es fundamental conocer y comprender el estado del arte del desarrollo de vacunas para el control efectivo de esta zoonosis. Este artículo revisa los estudios experimentales centrados en el desarrollo de vacunas para el control de la toxocariasis, y se presta especial atención a los estudios epidemiológicos relevantes sobre la importancia de los caninos domésticos en la toxocariasis humana.


Resumo Com base na prevalência e no impacto na saúde pública, a toxocaríase é uma zoonose subestimada nos países em desenvolvimento e desenvolvidos. A transmissão de Toxocara spp. envolve animais cães e gatos de estimação e vadios (Canis familiaris e Felis catus, respectivamente), que espalham os ovos do parasita nas fezes para o meio ambiente. Um dos principais fatores de risco para a infecção e desenvolvimento da toxocaríase humana é coabitar com filhotes de cachorros e gatos. Por um longo tempo, a estratégia preventiva para essa infecção parasitária tem sido o uso regular de medicamentos antiparasitários para reduzir a carga parasitária a curto prazo. Uma proteção imunológica duradoura pode ser alcançada com a vacinação, no entanto, uma vacina ainda não está disponível. Portanto, é fundamental conhecer e entender o estado da arte do desenvolvimento de vacinas para o controle efetivo dessa zoonose. Este artigo revisa os estudos experimentais focados no desenvolvimento de vacinas para o controle da toxocaríase, e atenção especial é dada a estudos epidemiológicos relevantes sobre a importância dos cães na toxocaríase humana.

11.
Vaccine ; 38(30): 4762-4772, 2020 06 19.
Artigo em Inglês | MEDLINE | ID: mdl-32451213

RESUMO

Toxocariasis, a natural helminth infection of dogs and cats caused by Toxocara canis and T. cati, respectively, that are transmitted to mammals, including humans. Infection control is based currently on periodic antihelmintic treatment and there is a need for the development of vaccines to prevent this infection. MATERIALS AND METHODS: Eight potential vaccine candidate T. canis recombinant proteins were identified by in silico (rTcGPRs, rTcCad, rTcVcan, rTcCyst) and larval proteomics (rTES26, rTES32, rMUC-3 and rCTL-4) analyses. Immunogenicity and protection against infectious challenge for seven of these antigens were determined in a murine model of toxocariasis. C57BL/6 female mice were immunized with each of or combinations of recombinant antigens prior to challenge with 500 T. canis embryonated eggs. Levels of specific antibodies (IgG, IgG1, IgG2a and IgE) in sera and cytokines (IL-5, INF-É£ and IL-10) produced by antigens-stimulated splenocytes, were measured. Presence of specific antibodies to the molecules was measured in sera of T. canis-seropositive dogs and humans. RESULTS: All seven molecules were immunogenic in immunized mice; all stimulated significantly elevated levels of specific IgG, IgG1 or IgG2a and six were associated with elevated levels of specific IgE; all induced elevated production of IFN- É£ and IL-10 by splenocytes, but only the in silico-identified membrane-associated recombinants (rTcCad, rTcVcan, and rTcCyst) induced significantly increased IL-5 production. Vaccination with two of the latter (rTcCad and rTcVcan) reduced larval loads in the T. canis challenged mice by 54.3% and 53.9% (P < 0.0001), respectively, compared to unimmunized controls. All seven recombinants were recognized by T. canis-seropositive dog and human sera. CONCLUSION: The identification of vaccine targets by in silico analysis was an effective strategy to identify immunogenic T. canis proteins capable of reducing larval burdens following challenge with the parasite. Two recombinant proteins, rTcCad and rTcVcan, were identified as promising vaccine candidates for canine toxocariasis.


Assuntos
Doenças do Gato , Doenças do Cão , Toxocara canis , Toxocaríase , Animais , Gatos , Modelos Animais de Doenças , Cães , Feminino , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Recombinantes/genética , Toxocaríase/prevenção & controle
12.
Clin Gastroenterol Hepatol ; 18(6): 1381-1392, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32068150

RESUMO

Recent evidence points to a plausible role of diet and the microbiome in the pathogenesis of both Crohn's disease (CD) and Ulcerative Colitis (UC). Dietary therapies based on exclusion of table foods and replacement with nutritional formulas and/or a combination of nutritional formulas and specific table foods may induce remission in CD. In UC, specific dietary components have also been associated with flare of disease. While evidence of varying quality has identified potential harmful or beneficial dietary components, physicians and patients at the present time do not have guidance as to which foods are safe, may be protective or deleterious for these diseases. The current document has been compiled by the nutrition cluster of the International Organization for the Study of Inflammatory Bowel Diseases (IOIBD) based on the best current evidence to provide expert opinion regarding specific dietary components, food groups and food additives that may be prudent to increase or decrease in the diet of patients with inflammatory bowel diseases to control and prevent relapse of inflammatory bowel diseases.


Assuntos
Colite Ulcerativa , Doença de Crohn , Doenças Inflamatórias Intestinais , Microbiota , Dieta , Humanos
13.
Curr Treat Options Gastroenterol ; 17(2): 313-325, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30968340

RESUMO

PURPOSE OF REVIEW: Diet plays an integral role in development of inflammatory bowel disease (IBD) and continues to act as a mediator of intestinal inflammation once disease sets in. Most clinicians provide little dietary guidance to IBD patients, in part due to lack of knowledge in nutrition and lack of available nutritional resources. The purpose of this review is to provide clinicians with a brief summary of the latest evidence behind diets popular among IBD patients, to highlight diets with known efficacy, and to provide guidance that may help busy practitioners. RECENT FINDINGS: The latest studies show that exclusive enteral nutrition (EEN) remains the most effective diet for induction of remission in Crohn's disease (CD), either in the form of elemental, semi-elemental, or polymeric formulas. Recent studies also show that EEN can be useful in complicated CD including in enterocutaneous fistulas closure and to optimize nutrition in the pre-operative setting. Although new studies suggest that partial enteral nutrition supplemented with elimination diets may be beneficial in ulcerative colitis (UC) and CD, larger controlled studies are needed to support their use. The autoimmune diet also shows promise but lacks larger studies. Recent uncontrolled clinical studies evaluating the specific carbohydrate diet (SCD) suggest that this diet may improve biochemical markers of inflammation and induce mucosal healing, although larger studies are needed to support its use, especially because the SCD is very restrictive. Short-term use of the low FODMAP diet is appropriate when in the setting of an acute flare up and/or in stricturing disease, but long-term restriction of FODMAPs is not recommended given long-term changes observed in the microbiome. Recent studies suggest that avoidance of processed foods, packaged with preservatives and emulsifiers, may be important in decreasing intestinal inflammation; many of the recent popular diets share a common concept, avoidance of processed foods. In this review of the latest literature, we highlight that dietary studies are still in a rudimentary stage. Large prospective randomized control studies are underway evaluating head to head comparisons on the efficacy of some of these diets. We offer general guiding principles that may help gastroenterologists in the meantime.

14.
Environ Sci Pollut Res Int ; 22(22): 17475-85, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26160124

RESUMO

Nematode parasites of the Anisakides family are often found in people living in countries where fish is consumed raw or partially cooked. This research shows the histological changes in the liver and spleen of Mugil incilis, collected in Cartagena Bay. These changes are associated with pollution by organochlorine pesticides and their possible influence on the parasite. Organochlorine compounds were extracted using the headspace-solid-phase microextraction (HS-SPME) technique. Residual amounts in the muscle of M. incilis such as ß-HCH, γ-HCH, heptachlor, aldrin, endosulfan, 4,4'-DDE, and dieldrin, among others, were identified by gas chromatography connected to an electron capture detector, indicating that the fauna of Cartagena Bay are exposed to these pollutants. Histological analysis was carried out on liver and spleen samples of M. incilis which were fixed, processed, and embedded in paraffin. The presence of melano-macrophages, granulomes, and trematodes in the liver was the most important changes observed. Larval prevalence for the Anisakis spp. was determined to be 1.6%; for Pseudoterranova spp., 25.3%, and for Contracaecum spp., 57.8%. Other parasites such as acanthocephalans were also reported for a total of 15.3%. Nevertheless, no significant correlation between parasites and organochlorines was found. This study is the first to correlate the presence of organochlorine compounds and histological damage in the liver and spleen of M. incilis, with the presence of parasites in fish from Cartagena Bay (Colombia).


Assuntos
Hidrocarbonetos Clorados/análise , Praguicidas/análise , Smegmamorpha , Poluentes Químicos da Água/análise , Animais , Oceano Atlântico , Colômbia
15.
Pharmacol Biochem Behav ; 128: 23-32, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25449358

RESUMO

Metabotropic P2Y receptors subfamily consists of eight functional mammalian receptors. Specifically, P2Y1, P2Y6 and P2Y11 receptors have been described in the sensory nervous system, but their participation, at peripheral level, in behavioral pain models is scarcely understood. This study assessed the role of peripheral P2Y1, P2Y6 and P2Y11 receptors in formalin-induced inflammatory pain. Ipsilateral, but not contralateral peripheral pre-treatment with the endogenous P2Y1 (ADP, 100-1000nmol/paw), P2Y6 (UDP, 180-300nmol/paw) and P2Y11 (ATP, 100-1000nmol/paw), or selective P2Y1 (MRS2365, 0.1-10nmol/paw), P2Y6 (PSB0474, 0.1-0.10pmol/paw) and P2Y11 (NF546, 0.3-3nmol/paw) receptor agonists increased 0.5% formalin-induced flinching behavior. Concordantly, peripheral pre-treatment with the selective P2Y1 (MRS2500, 0.01-10pmol/paw), P2Y6 (MRS2578, 3-30nmol/paw) and P2Y11 (NF340, 1-10nmol/paw) receptor antagonists significantly decreased 1% formalin-induced flinching behavior. Furthermore, the pronociceptive effect of ADP (100nmol/paw) or MRS2365 (10nmol/paw), UDP (300nmol/paw) or PSB0474 (10pmol/paw) and ATP (1000nmol/paw) or NF546 (3nmol/paw) was blocked by the selective P2Y1 (MRS2500, 0.01nmol/paw), P2Y6 (MRS2578, 3nmol/paw), and P2Y11 (NF340, 1nmol/paw) receptor antagonists, respectively. Western blot analysis confirmed the presence of P2Y1 (66kDa), P2Y6 (36kDa) and P2Y11 (75kDa) receptors in dorsal root ganglia (DRG) and sciatic nerve. Results suggest that peripheral activation of P2Y1, P2Y6 and P2Y11 receptors plays a pronociceptive role in formalin-induced pain.


Assuntos
Dor Nociceptiva/fisiopatologia , Receptores Purinérgicos P2Y1/fisiologia , Receptores Purinérgicos P2/fisiologia , Difosfato de Adenosina/metabolismo , Trifosfato de Adenosina/metabolismo , Animais , Feminino , Formaldeído/toxicidade , Gânglios Espinais/efeitos dos fármacos , Gânglios Espinais/fisiopatologia , Inflamação/fisiopatologia , Isotiocianatos/farmacologia , Nociceptividade/efeitos dos fármacos , Nociceptividade/fisiologia , Dor Nociceptiva/induzido quimicamente , Nociceptores/efeitos dos fármacos , Nociceptores/fisiologia , Agonistas do Receptor Purinérgico P2/farmacologia , Antagonistas do Receptor Purinérgico P2/farmacologia , Ratos , Ratos Wistar , Nervo Isquiático/efeitos dos fármacos , Nervo Isquiático/fisiopatologia , Tioureia/análogos & derivados , Tioureia/farmacologia , Difosfato de Uridina/análogos & derivados , Difosfato de Uridina/metabolismo , Difosfato de Uridina/farmacologia
17.
VozAndes ; 13(1): 7-13, ene. 2000. graf, tab
Artigo em Espanhol | LILACS | ID: lil-278898

RESUMO

El plomo es el contaminante ambiental más peligroso por sus efectos en el crecimiento y desarrollo de los niños. En 1991, una investigación de Fundación Natura demostró un alto nivel de contaminación ambiental que ocasionaba 40 por ciento de exceso de plomo en sangre en los recién nacidos y 180 por ciento en los escolares en Quito. La presente investigación amplió su área de estudio a la ciudades de Cuenca y Guayaquil con el objeto de efectuar un monitoreo al nivel de las principales ciudades. Los resultados indican que existe una disminución significativa del nivel de plomo, de tal manera que para 1998 los niños que nacen en Quito y Guayaquil tienen valores normales. En Cuenca todavía hay un 6.6 por ciento en riesgo...


Assuntos
Monitoramento Ambiental , Chumbo , Poluição Ambiental
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