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1.
Reumatol. clín. (Barc.) ; 19(6): 319-327, Jun-Jul. 2023. tab, graf
Artigo em Inglês | IBECS | ID: ibc-221271

RESUMO

Objective: To describe efficacy, safety, and patient-reported outcomes (PROs) in patients with rheumatoid arthritis (RA) with an inadequate response to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) treated with tofacitinib or biological DMARDs (bDMARDs) in real-life conditions. Methods: A noninterventional study was performed between March 2017 and September 2019 at 13 sites in Colombia and Peru. Outcomes measured at baseline and at the 6-month follow-up were disease activity (RAPID3 [Routine Assessment of Patients Index Data] score), functional status (HAQ-DI [Health Assessment Questionnaire] score), and quality of life (EQ-5D-3L [EuroQol Questionnaire]). The Disease Activity Score-28 (DAS28-ESR) and frequency of adverse events (AEs) were also reported. Unadjusted and adjusted differences from baseline were estimated and expressed as the least squares mean difference (LSMD). Results: Data from 100 patients treated with tofacitinib and 70 patients with bDMARDs were collected. At baseline, the patients’ mean age was 53.53 years (SD 13.77), the mean disease duration was 6.31 years (SD 7.01). The change from baseline at month 6 was not statistically significant different in the adjusted LSMD [SD] for tofacitinib vs. bDMARDs for RAPID3 score (−2.55[.30] vs. −2.52[.26]), HAQ-DI score (−.56[.07] vs. −.50[.08]), EQ-5D-3L score (.39[.04] vs. .37[.04]) and DAS28-ESR (−2.37[.22] vs. −2.77[.20]). Patients from both groups presented similar proportions of nonserious and serious AEs. No deaths were reported.Conclusion: Changes from baseline were not statistically significantly different between tofacitinib and bDMARDs in terms of RAPID3 scores and secondary outcomes. Patients from both groups presented similar proportions of nonserious and serious AEs.(AU)


Objetivo: Describir la eficacia, la seguridad y los desenlaces reportados por los pacientes (PRO) en pacientes con artritis reumatoide (RA) con una respuesta inadecuada a los fármacos antirreumáticos modificadores de la enfermedad sintéticos convencionales (csFARME) tratados con tofacitinib o FARME biológico (bFARME) en condiciones de la vida real. Métodos: Estudio no intervencional realizado entre marzo de 2017 y septiembre de 2019 en 13 centros de Colombia y Perú. Los desenlaces evaluados al inicio y a los seis meses de seguimiento fueron la actividad de la enfermedad (puntaje Routine Assessment of Patients Index Data [RAPID3]), el estado funcional (puntaje Health Assessment Questionnaire [HAQ-DI]) y la calidad de vida (EuroQol Questionnaire [EQ-5D-3L]). El puntaje de actividad de la enfermedad-28 (DAS28-ESR) y la frecuencia de eventos adversos (EA). Se estimaron las diferencias no ajustadas y ajustadas con respecto a los valores basales y se expresaron como diferencia de medias por mínimos cuadrados (LMD). Resultados: Se recolectó información de 100 pacientes tratados con tofacitinib y 70 pacientes con bFARME. Al inicio del estudio, la edad media de los pacientes era de 53,53 años (DE 13,77) y la duración media de la enfermedad de 6,31 años (DE 7,01). El cambio con respecto al valor basal en el mes 6 no fue estadísticamente significativo en la LMD ajustada (SE) para tofacitinib vs. los bFARME para RAPID3 (−2,55 [0,30] vs. −2,52 [0,26]), puntuación HAQ-DI (−0,56 [0,07] vs. −0,50 [0,08]), puntuación EQ-5D-3L (0,39 [0,04] vs. 0,37 [0,04]) y DAS28-ESR (−2,37 [0,22] vs. −2,77 [0,20]). Los pacientes de ambos grupos presentaron proporciones similares de EA no graves y graves. Ninguna muerte fue reportada. Conclusiones: Los cambios desde el inicio no fueron estadísticamente significativos entre tofacitinib y los bFARME en RAPID3 y en los desenlaces secundarios. Los pacientes de ambos grupos presentaron proporciones similares de EA no graves y graves.(AU)


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Artrite Reumatoide/tratamento farmacológico , Antirreumáticos , Avaliação de Resultados em Cuidados de Saúde , Colômbia , Peru , Reumatologia , Doenças Reumáticas
2.
Reumatol Clin (Engl Ed) ; 19(6): 319-327, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37286268

RESUMO

OBJECTIVE: To describe efficacy, safety, and patient-reported outcomes (PROs) in patients with rheumatoid arthritis (RA) with an inadequate response to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) treated with tofacitinib or biological DMARDs (bDMARDs) in real-life conditions. METHODS: A noninterventional study was performed between March 2017 and September 2019 at 13 sites in Colombia and Peru. Outcomes measured at baseline and at the 6-month follow-up were disease activity (RAPID3 [Routine Assessment of Patients Index Data] score), functional status (HAQ-DI [Health Assessment Questionnaire] score), and quality of life (EQ-5D-3L [EuroQol Questionnaire]). The Disease Activity Score-28 (DAS28-ESR) and frequency of adverse events (AEs) were also reported. Unadjusted and adjusted differences from baseline were estimated and expressed as the least squares mean difference (LSMD). RESULTS: Data from 100 patients treated with tofacitinib and 70 patients with bDMARDs were collected. At baseline, the patients' mean age was 53.53 years (SD 13.77), the mean disease duration was 6.31 years (SD 7.01). The change from baseline at month 6 was not statistically significant different in the adjusted LSMD [SD] for tofacitinib vs. bDMARDs for RAPID3 score (-2.55[.30] vs. -2.52[.26]), HAQ-DI score (-.56[.07] vs. -.50[.08]), EQ-5D-3L score (.39[.04] vs. .37[.04]) and DAS28-ESR (-2.37[.22] vs. -2.77[.20]). Patients from both groups presented similar proportions of nonserious and serious AEs. No deaths were reported. CONCLUSION: Changes from baseline were not statistically significantly different between tofacitinib and bDMARDs in terms of RAPID3 scores and secondary outcomes. Patients from both groups presented similar proportions of nonserious and serious AEs. CLINICAL TRIAL NUMBER: NCT03073109.


Assuntos
Antirreumáticos , Artrite Reumatoide , Humanos , Pessoa de Meia-Idade , Qualidade de Vida , América Latina , Resultado do Tratamento , Pirróis/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Medidas de Resultados Relatados pelo Paciente
3.
Arch Oral Biol ; 146: 105602, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36543038

RESUMO

OBJECTIVE: The aims of this study were to develop a novel rodent model of masticatory muscle ischaemia via unilateral ligation of the external carotid artery (ECA), and to undertake a preliminary investigation to characterize its downstream effects on mechanosensitivity and cellular features of the masseter and temporalis muscles. DESIGN: The right ECA of 18 male Sprague-Dawley rats was ligated under general anaesthesia. Mechanical detection thresholds (MDTs) at the masseter and temporalis bilaterally were measured immediately before ECA ligation and after euthanasia at 10-, 20-, and 35-days (n = 6 rats/timepoint). Tissue samples from both muscles and sides were harvested for histological analyses and for assessing changes in the expression of markers of hypoxia and muscle degeneration (Hif-1α, VegfA, and Fbxo32) via real time PCR. Data were analyzed using mixed effect models and non-parametric tests. Statistical significance was set at p < 0.05. RESULTS: MDTs were higher in the right than left hemiface (p = 0.009) after 20 days. Histological changes indicative of muscle degeneration and fibrosis were observed in the right muscles. Hif-1α, VegfA, and Fbxo32 were more highly expressed in the masseter than temporalis muscles (all p < 0.05). Hif-1α and, VegfA did not change significantly with time in all muscles (all p > 0.05). Fbxo32 expression gradually increased in the right masseter (p = 0.024) and left temporalis (p = 0.05). CONCLUSIONS: ECA ligation in rats induced hyposensitivity in the homolateral hemiface after 20 days accompanied by tissue degenerative changes. Our findings support the use of this model to study pathophysiologic mechanisms of masticatory muscle ischaemia in larger investigations.


Assuntos
Mastigação , Músculos da Mastigação , Masculino , Ratos , Animais , Ratos Sprague-Dawley , Mastigação/fisiologia , Eletromiografia , Músculos da Mastigação/fisiologia , Músculo Temporal , Músculo Masseter
4.
Expert Rev Pharmacoecon Outcomes Res ; 22(5): 787-794, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35249439

RESUMO

OBJECTIVE: To evaluate work productivity of adult Latin American patients with rheumatoid arthritis (RA) treated with tofacitinib and biological disease-modifying anti-rheumatic drugs (bDMARDs) measured by the Work Productivity and Activity Impairment (WPAI) in RA questionnaire at 0- and 6-month follow-up. METHODS: This non-interventional study was performed in Colombia and Peru. Evaluated the effects of tofacitinib and bDMARDs in patients with RA after failure of conventional DMARDs. The WPAI-RA questionnaire was administered at baseline and at the 6-month (±1 month) follow-up. The results are expressed as least squares means (LSMs), and standard errors (SEs). RESULTS: One hundred patients treated with tofacitinib and 70 patients treated with bDMARDs were recruited. Twenty-eight percent of patients from the tofacitinib group and 40.0% from the bDMARDs group were working for pay at baseline. At month 6, the changes in absenteeism, presenteeism, and work impairment due to health were -18.3% (SE 7.7), -34.8% (SE 5.9), and -11.0% (SE 16.5), respectively, in the tofacitinib group and -19.4% (SE 8.0), -34.8% (SE 6.2), and -15.9% (SE 15.0), for the bDMARD group. CONCLUSION: For patients who reported working, there were improvements in presenteeism, absenteeism, and work impairment due to health in both groups. TRIAL REGISTRATION: NCT03073109.


Assuntos
Antirreumáticos , Artrite Reumatoide , Adulto , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Eficiência , Humanos , América Latina , Piperidinas/uso terapêutico , Pirimidinas/uso terapêutico , Pirróis/efeitos adversos , Resultado do Tratamento , Desempenho Profissional
5.
Childs Nerv Syst ; 37(11): 3549-3554, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34184098

RESUMO

INTRODUCTION: The TROPHY registry has been established to conduct an international multicenter prospective data collection on the surgical management of neonatal intraventricular hemorrhage (IVH)-related hydrocephalus to possibly contribute to future guidelines. The registry allows comparing the techniques established to treat hydrocephalus, such as external ventricular drainage (EVD), ventricular access device (VAD), ventricular subgaleal shunt (VSGS), and neuroendoscopic lavage (NEL). This first status report of the registry presents the results of the standard of care survey of participating centers assessed upon online registration. METHODS: On the standard of treatment forms, each center indicated the institutional protocol of interventions performed for neonatal post-hemorrhagic hydrocephalus (nPHH) for a time period of 2 years (Y1 and Y2) before starting the active participation in the registry. In addition, the amount of patients enrolled so far and allocated to a treatment approach are reported. RESULTS: According to the standard of treatment forms completed by 56 registered centers, fewer EVDs (Y1 55% Y2 46%) were used while more centers have implemented NEL (Y1 39%; Y2 52%) to treat nPHH. VAD (Y1 66%; Y2 66%) and VSGS (Y1 42%; Y2 41%) were used at a consistent rate during the 2 years. The majority of the centers used at least two different techniques to treat nPHH (43%), while 27% used only one technique, 21% used three, and 7% used even four different techniques. Patient data of 110 infants treated surgically between 9/2018 and 2/2021 (13% EVD, 15% VAD, 30% VSGS, and 43% NEL) were contributed by 29 centers. CONCLUSIONS: Our results emphasize the varying strategies used for the treatment of nPHH. The international TROPHY registry has entered into a phase of growing patient recruitment. Further evaluation will be performed and published according to the registry protocol.


Assuntos
Hidrocefalia , Neuroendoscopia , Hemorragia Cerebral/epidemiologia , Hemorragia Cerebral/cirurgia , Humanos , Hidrocefalia/epidemiologia , Hidrocefalia/cirurgia , Lactente , Recém-Nascido , Neuroendoscópios , Sistema de Registros
6.
Brain Res ; 1758: 147303, 2021 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-33516813

RESUMO

Mesial temporal lobe epilepsy (mTLE) is the most common epilepsy induced by previous cerebral injury, and one out of three mTLE patients develops drug resistance (DR). AIM: To assess the expression of Bcl-2, Caspase-3, Caspase-9, IL1-ß, SEMA-3a, NT-3 and P-glycoprotein in the temporal cortex and their relationship with the progression of mTLE-DR clinical features in patients with mTLE-DR. METHOD: Tissue samples from 17 patients were evaluated for protein expression by Western blot and the relationships of the evaluated proteins with the clinical features of the mTLE were assessed through hierarchical cluster analysis. RESULTS: The mTLE-DR group showed significantly higher P-glycoprotein, Bcl-2 and Caspase-9 levels ***p < 0.0001, ****p < 0.0001 and ***p < 0.0002, respectively, than the autopsy control group. Four patient clusters were identified: Clusters 1 and 3 showed relationships among the age of mTLE onset, duration of mTLE-DR, average number of epileptic seizures per week, number of previous antiepileptic drugs (AEDs) and increased expression of Caspase-3, Caspase-9, Neurotrophin-3 and Semaphorin-3a. Clusters 2 and 4 showed relationships among the mTLE onset age, current age, average number of epileptic seizures per week, number of previous AEDs and increased expression of IL1-ß, Bcl-2, P-glycoprotein, Caspase-3 and NT-3. CONCLUSION: The relationships among the clinical data the age of mTLE onset, DR duration, number of previous AEDs, and average number of seizures per week and the expression of proteins involved in neuronal death, neuroinflammation and aberrant connection formation, as which are biological markers in the cerebral temporal cortex, are important factors in the progression and severity of mTLE-DR and support the intrinsic severity hypothesis.


Assuntos
Biomarcadores/análise , Biomarcadores/metabolismo , Epilepsia Resistente a Medicamentos/metabolismo , Epilepsia do Lobo Temporal/metabolismo , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Adulto , Idoso , Caspase 3/metabolismo , Caspase 9/metabolismo , Feminino , Humanos , Interleucina-1beta/metabolismo , Masculino , Pessoa de Meia-Idade , Neurotrofina 3/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Semaforina-3A/metabolismo , Adulto Jovem
7.
Gac. méd. boliv ; 43(2): 120-126, dic. 2020. ilus
Artigo em Espanhol | LILACS | ID: biblio-1249991

RESUMO

En diferentes regiones de Latinoamérica la infección por T. cruzi y Leishmania se superponen, por lo cual se reportan infecciones mixtas circulantes, debido a esto; deben realizarse pruebas diagnósticas específicas para evitar reacciones cruzadas entre estas dos patologías. OBJETIVO: determinar patrones de fluorescencia que permitan la diferenciación entre Leishmaniasis, enfermedad de Chagas e infección mixta empleando epimastigotes de T. cruzi. MÉTODOS: se empleó la técnica de Inmunofluorescencia Indirecta utilizando epimastigotes de T. cruzi (TcV autóctono) como antígeno figurado frente a un panel de muestras de suero codificados como A, B, C y D correspondientes a pacientes con infección por: Leishmaniasis (A), Infección mixta por Leishmania y Chagas(B), Enfermedad de Chagas (C) y sin ninguna de las dos infecciones (D). RESULTADOS: en los cuatro paneles de muestras se observaron diferentes patrones de intensidad de fluorescencia a nivel de membrana y núcleo de los epimastigotes de T. cruzi (TcV autóctono). CONCLUSIONES: la técnica de Inmunofluorescencia (IFI) con antígenos de epimastigotes de T. cruzi a demostrado utilidad en la diferenciación entre enfermedad de Chagas, Leishmaniasis y/o infecciones mixtas por ambos parásitos en aquellas zonas donde la coexistencia de ambas es habitual


In different regions of Latin America, infection by T. cruzi and Leishmania overlap, for which mixed circulating infections are reported, due to this; Specific diagnostic tests must be performed to avoid cross reactions between these two pathologies. OBJECTIVE: to determine fluorescence patterns that allow the differentiation between Leishmaniasis, Chagas disease and mixed infection using T. cruzi epimastigotes. METHODS: the Indirect Immunofluorescence technique was used using epimastigotes of T. cruzi (autochthonous TcV) as figurative antigen against a panel of serum samples coded as A, B, C and D corresponding to patients with infection by: Leishmaniasis (A) , Mixed infection by Leishmania and Chagas (B), Chagas disease (C) and without either of the two infections (D). RESULTS: in the four sample panels, different patterns of fluorescence intensity were observed at the membrane and nucleus level of the epimastigotes of T. cruzi (autochthonous TcV). CCONCLUSIONS: the Immunofluorescence technique (IFI) with T. cruzi epimastigote antigens has proven useful in differentiating between Chagas disease, Leishmaniasis and / or mixed infections by both parasites in areas where the coexistence of both is common.


Assuntos
Humanos , Trypanosoma cruzi , Leishmaniose , Fluorescência , Parasitos , Doença de Chagas , Infecções
8.
9.
Poult Sci ; 99(9): 4514-4520, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32867995

RESUMO

Rye is high in nonstarch polysaccharides (NSP), a complex carbohydrate which cannot be digested by poultry as they lack the endogenous enzymes to do so. Exogenous carbohydrases must therefore be supplemented to avoid the antinutritional effects associated with a high NSP diet. The objectives of the present study were to evaluate the effects of a rye-based diet with and without supplementation of a Bacillus direct-fed microbial (DFM) on body weight, bone mineralization, and leaky gut, as well as its role on influencing serum concentrations of peptide YY (PPY) and the ammonia concentration in turkey manure. Two independent trials were conducted. In each experiment, day-of-hatch female turkey poults were neck tagged and randomly assigned to either a control rye-based diet or a rye-based diet supplemented with the DFM (n = 25 birds/group). At 10 days-of-age, poults in both groups were administered with an appropriate dose of fluorescein isothiocyanate-dextran (FITC-d) by oral gavage. One hour later, all poults were euthanized. Blood was collected to evaluate serum FITC-d and PPY concentrations. Furthermore, in Trial 2 only, both tibias were removed for assessment of bone parameters, and turkey manure was collected to evaluate physicochemical analysis. In both trials, poults treated with the DFM showed a significant increase (P < 0.05) in body weight and body weight gain as compared with control nontreated poults. Poults that received the DFM also had a significant reduction in serum levels of PPY and FITC-d when compared with control nontreated poults. In Trial 2, turkeys treated with the DFM had a substantial increase in tibia strength, tibia diameter, total ash, calcium, and phosphorus when compared with control nontreated turkeys. Their manure was also shown to have a significant reduction in the concentration of ammonia. This is the first report of a commercial DFM reducing the concentration of this compound in turkey manure. In summary, the results of the present study confirm that turkeys fed with a rye-based diet have a significant increase in gut permeability, a reduced body weight, and decreased bone mineralization when compared with turkeys fed with the DFM. Turkeys that received the rye-based diet supplemented with the Bacillus-DFM also had a significant reduction in the serum concentration of PPY when compared with control turkeys. This finding suggests a possible prebiotic effect of rye, warranting future studies to test this effect. Further studies to evaluate the microbiota diversity, as well as the concentration of ceca short-chain fatty acids, are also necessary to confirm the reliability of PPY as a potential metabolomic biomarker in poultry.


Assuntos
Amônia , Bacillus , Calcificação Fisiológica , Peptídeo YY , Probióticos , Perus , Amônia/metabolismo , Ração Animal/análise , Animais , Animais Recém-Nascidos , Calcificação Fisiológica/fisiologia , Dieta/veterinária , Feminino , Peptídeo YY/sangue , Distribuição Aleatória , Reprodutibilidade dos Testes , Secale
12.
Nat Commun ; 11(1): 344, 2020 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-31953396

RESUMO

The achievement of high growth rates in YBa2Cu3O7 epitaxial high-temperature superconducting films has become strategic to enable high-throughput manufacturing of long length coated conductors for energy and large magnet applications. We report on a transient liquid assisted growth process capable of achieving ultrafast growth rates (100 nm s-1) and high critical current densities (5 MA cm-2 at 77 K). This is based on the kinetic preference of Ba-Cu-O to form transient liquids prior to crystalline thermodynamic equilibrium phases, and as such is a non-equilibrium approach. The transient liquid-assisted growth process is combined with chemical solution deposition, proposing a scalable method for superconducting tapes manufacturing. Additionally, using colloidal solutions, the growth process is extended towards fabrication of nanocomposite films for enhanced superconducting properties at high magnetic fields. Fast acquisition in situ synchrotron X-ray diffraction and high resolution scanning transmission electron microscopy (STEM) become crucial measurements in disentangling key aspects of the growth process.

13.
Mycotoxin Res ; 36(1): 31-39, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31297722

RESUMO

The effect of dietary aflatoxin B1 (AFB1) and Salmonella Enteritidis infection on intestinal permeability was investigated. Two hundred 1-day-old male Ross 308 broiler chickens were randomly divided into 4 treatments of 5 replicates each (10 birds per replicate), which were fed ad libitum for 3 weeks with the following treatments: control, chickens fed an AFB1-free diet; AF, chickens fed an AFB1-contaminated diet at 470 ng/g; SE, chickens fed an AFB1-free diet and challenged with 108 cfu of S. Enteritidis per bird at 18 days old; AF + SE, chickens fed an AFB1-contaminated diet and challenged with 108 cfu of S. Enteritidis per bird at 18 days old. At day 21 of age, chicks received an oral gavage dose of fluorescein isothiocyanate dextran (FITC-dextran) to evaluate gastrointestinal leakage. Blood and intestinal samples were collected to evaluate serum biochemistry and total intestinal IgA secretion, respectively. Liver tissues were aseptically collected to assess bacterial invasiveness and for histomorphological studies. The results showed that chickens receiving AFB1 presented a significant increment (up to 2.4-fold) in serum FITC-dextran concentration (p < 0.05). Nevertheless, S. Enteritidis infection had no additional effect on gastrointestinal leakage. Furthermore, the ingestion of AFB1 had no impact on the invasive potential of S. Enteritidis. These results suggest that moderate-dose AFB1 adversely affects intestinal barrier function resulting in increased gut permeability in broiler chickens.


Assuntos
Aflatoxina B1 , Intestinos/patologia , Permeabilidade/efeitos dos fármacos , Salmonella enteritidis/patogenicidade , Aflatoxina B1/administração & dosagem , Aflatoxina B1/efeitos adversos , Aflatoxina B1/toxicidade , Ração Animal/análise , Animais , Galinhas , Dieta/veterinária , Fígado/efeitos dos fármacos , Fígado/microbiologia , Fígado/patologia , Doenças das Aves Domésticas , Salmonelose Animal
14.
Rev Neurol ; 69(8): 352, 2019 10 16.
Artigo em Espanhol | MEDLINE | ID: mdl-31588992

RESUMO

TITLE: Nuevas evidencias y retos sobre neuropatia optica inflamatoria recurrente cronica.


Assuntos
Doenças do Nervo Óptico , Humanos , Nervo Óptico , Recidiva
16.
Lung Cancer ; 135: 230-233, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31235316

RESUMO

OBJECTIVES: To investigate the capacity of a trained dog to identify LC in patients with malignant SPN. METHODS: We collected 90 exhaled gas samples from 30 patients with SPN (3 samples/patient). As controls we used 61 healthy volunteers and 18 COPD patients without SNP or LC, in each of whom we collected 5 exhaled gas samples (n = 395). The dog (Blat, a 4-year-old crossbreed between a Labrador Retriever and a Pitbull) and the methodology used were the same as previously reported by our group (see: https://drive.google.com/open?id=1R4mOtOtuZkTeb5iOEEv0K9r2kHKlPhWd). RESULTS: Of 30 patients with SPN, Blat recognized 27 of them as positive for LC and 3 as negative for LC. These results fully matched post-surgical pathological results. Sensibility was 0.97, Specificity 0.99, Positive Predictive value 0.97 and negative predictive value 0.99. The AUC of the ROC curve was 0.985. CONCLUSIONS: Trained dogs can identify accurately the malignant origin of SPN. It is now time to develop technology that can match canine olfaction and facilitate the implementation of this diagnostic approach in the clinic.


Assuntos
Neoplasias Pulmonares/diagnóstico , Nódulo Pulmonar Solitário/diagnóstico , Idoso , Animais , Estudos de Casos e Controles , Diagnóstico Diferencial , Modelos Animais de Doenças , Cães , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Gradação de Tumores/métodos , Curva ROC , Reprodutibilidade dos Testes , Nódulo Pulmonar Solitário/patologia
17.
Int Rev Cell Mol Biol ; 345: 35-136, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30904196

RESUMO

Innate immunity, the first line of defense against invading pathogens, is an ancient form of host defense found in all animals, from sponges to humans. During infection, innate immune receptors recognize conserved molecular patterns, such as microbial surface molecules, metabolites produces during infection, or nucleic acids of the microbe's genome. When initiated, the innate immune response activates a host defense program that leads to the synthesis proteins capable of pathogen killing. In mammals, the induction of cytokines during the innate immune response leads to the recruitment of professional immune cells to the site of infection, leading to an adaptive immune response. While a fully functional innate immune response is crucial for a proper host response and curbing microbial infection, if the innate immune response is dysfunctional and is activated in the absence of infection, autoinflammation and autoimmune disorders can develop. Therefore, it follows that the innate immune response must be tightly controlled to avoid an autoimmune response from host-derived molecules, yet still unencumbered to respond to infection. In this review, we will focus on the innate immune response activated from cytosolic nucleic acids, derived from the microbe or host itself. We will depict how viruses and bacteria activate these nucleic acid sensing pathways and their mechanisms to inhibit the pathways. We will also describe the autoinflammatory and autoimmune disorders that develop when these pathways are hyperactive. Finally, we will discuss gaps in knowledge with regard to innate immune response failure and identify where further research is needed.


Assuntos
Doenças Autoimunes/imunologia , Ácidos Nucleicos/metabolismo , Animais , Autoimunidade , DNA/imunologia , Humanos , Transdução de Sinais , Vírus/imunologia
18.
Cell Rep ; 23(12): 3537-3550.e6, 2018 06 19.
Artigo em Inglês | MEDLINE | ID: mdl-29924997

RESUMO

The vertebrate protein STING, an intracellular sensor of cyclic dinucleotides, is critical to the innate immune response and the induction of type I interferon during pathogenic infection. Here, we show that a STING ortholog (dmSTING) exists in Drosophila, which, similar to vertebrate STING, associates with cyclic dinucleotides to initiate an innate immune response. Following infection with Listeria monocytogenes, dmSTING activates an innate immune response via activation of the NF-κB transcription factor Relish, part of the immune deficiency (IMD) pathway. DmSTING-mediated activation of the immune response reduces the levels of Listeria-induced lethality and bacterial load in the host. Of significance, dmSTING triggers an innate immune response in the absence of a known functional cyclic guanosine monophosphate (GMP)-AMP synthase (cGAS) ortholog in the fly. Together, our results demonstrate that STING is an evolutionarily conserved antimicrobial effector between flies and mammals, and it comprises a key component of host defense against pathogenic infection in Drosophila.


Assuntos
Anti-Infecciosos/metabolismo , Sequência Conservada , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/metabolismo , Evolução Molecular , Proteínas de Membrana/metabolismo , Sequência de Aminoácidos , Animais , Peptídeos Catiônicos Antimicrobianos/metabolismo , Proteínas de Drosophila/química , Drosophila melanogaster/microbiologia , Listeria monocytogenes/fisiologia , Listeriose/microbiologia , Proteínas de Membrana/química , NF-kappa B/metabolismo , Nucleotídeos/metabolismo , Ligação Proteica , Transdução de Sinais , Fatores de Transcrição/metabolismo , Transcrição Gênica
19.
Rev Sci Tech ; 37(3): 907-924, 2018 Dec.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-30964470

RESUMO

Toxoplasmosis is one of the most widespread zoonoses in the world, due to the existence of a wide variety of Toxoplasma gondii hosts, which include several domestic animal species. In Cuba, there is sustained production of the Bubalus species, which is highly adaptable and disease resistant, although it has been identified as a reservoir for a range of aetiological agents. Several countries have reported buffaloes as the intermediate host of T. gondii, noting the need to carry out epidemiological studies and confirm the possible presence of this parasitic infection in the Bubalus species. The current study was conducted to validate an inhibition enzyme-linked immunosorbent assay (i/ELISA) system for the diagnosis of T. gondii infection in buffaloes (Bubalus bubalis). This involved evaluating its performance in relation to that of a latex agglutination test. With buffalo sera, the i/ELISA assay showed a sensitivity of 100%, a specificity of 99.5%,and a concordance of 0.99 (considered very good) with respect to the reference diagnostic method. The conclusion is that i/ELISA performs extremely well as a serological test for the diagnosis of T. gondii in buffaloes.


La toxoplasmose est l'une des zoonoses les plus répandues dans le monde, ce qui s'explique par le très large spectre d'hôtes de Toxoplasma gondii, dont plusieurs espèces d'animaux domestiques. À Cuba, les buffles font l'objet d'un élevage durable et présentent de bonnes aptitudes d'adaptation et de résistance aux maladies, bien que cette espèce joue un rôle avéré de réservoir pour un certain nombre d'agents pathogènes. Des rapports émanant de plusieurs pays ont fait état du rôle joué par les buffles en tant qu'hôtes intermédiaires de T. gondii, d'où la nécessité d'effectuer des études épidémiologiques afin de confirmer la présence éventuelle de cette parasitose chez cette espèce. Les auteurs présentent des résultats d'une étude de validation d'une méthode immuno-enzymatique d'inhibition des anticorps pour le diagnostic de T. gondii chez le buffle (Bubalusbubalis). Pour ce faire, les performances de cette méthode ont été évaluées par rapport à celles du test d'agglutination au latex. La comparaison à partir de sérums de buffles a montré que la sensibilité de l'épreuve immuno-enzymatique était de 100 % et sa spécificité de 99,5%, avec une concordance par rapport à la méthode de référence de 0,99, ce qui est considéré un très bon résultat. Cette étude démontre l'aptitude de l'ELISA d'inhibition pour le diagnostic sérologique de T. gondii chez le buffle et conclut à son excellente performance diagnostique.


La toxoplasmosis es una de las zoonosis más difundidas en el mundo debido a que existe una amplia variedad de hospedadores de Toxoplasma gondii, entre los que se encuentran varias de las especies de animales domésticos. En Cuba, la especie bufalina se produce de manera sostenida con buena adaptabilidad y resistencia a las enfermedades, aunque se ha identificado como reservorio de diversos agentes etiológicos. En varios países se ha informado que los búfalos son hospedadores intermediarios de T. gondii y se ha indicado la necesidad derealizar estudios epidemiológicos y de comprobar la posible presencia de dicha parasitosis en esta especie. Este trabajo se realizó para validar un sistema inmunoenzimático de inhibición de un anticuerpo (ELISA/i) para el diagnósticode infección por T. gondii en búfalos (Bubalus bubalis). Para ello, se evaluó su rendimiento respecto a una prueba de aglutinación por látex. Frente a sueros de búfalo, el sistema inmunoenzimático demostró tener una sensibilidad del 100%, una especificidad del 99,5% y una concordancia de 0,99, considerada muy buena, respecto al método de diagnóstico de referencia. Se concluye que el ELISA/i permite el diagnóstico serológico de T. gondii en búfalos con un excelente rendimiento diagnóstico.


Assuntos
Toxoplasmose Animal , Animais , Anticorpos Antiprotozoários , Búfalos , Ensaio de Imunoadsorção Enzimática
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