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BACKGROUND: The Post-COVID-19 Functional Status (PCFS) scale was created to assess the functional status of patients after hospital discharge due to COVID-19. OBJECTIVE: To perform cross-cultural adaptation of the PCFS Scale and Manual into Brazilian Portuguese and evaluate its measurement properties in patients post-COVID-19. METHODS: For the cross-cultural adaptation, independent translations and back-translations were performed. This was followed by a pre-test, with analysis of the Content Validity Index (CVI), and preparation of the final version, after evaluating the measurement properties. Spearman's correlation between the PCFS and the WHO Disability Classification Scheme (WHODAS 2.0) was used for convergent validity. Weighted Kappa (wκ) was used for test-retest and interobserver reliability for PCFS scores and Kappa (κ) for PCFS items. Internal consistency was assessed using Cronbach's alpha. Only patients with post-discharge COVID-19 were evaluated through video-conferencing platforms. RESULTS: The CVI was 0.75-0.83 for comprehension and 0.83-0.84 for the language of the self-administered questionnaire and the structured interview version. For measurement properties, 63 patients were evaluated, 68% male, 51.50 (12.60) years, 12.28 (7.62) days of hospitalization. For the convergent validity, a strong correlation was found (r = 0.73; p<0.01). The test-retest (wκ=0.54) and interobserver (wκ=0.43) reliability was moderate and the item-by-item analyzes ranged from fair to substantial (κ=0.25-0.66) and weak to substantial (κ=0.07-0.79). Internal consistency was excellent (0.85). CONCLUSION: The final PCFS in Brazilian Portuguese showed adequate content validity, reliability, internal consistency, and convergent validity for the functional assessment of patients after hospital discharge due to COVID-19.
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COVID-19 , Comparación Transcultural , Humanos , Masculino , Femenino , Brasil , Reproducibilidad de los Resultados , Cuidados Posteriores , Estado Funcional , Alta del Paciente , Encuestas y Cuestionarios , Traducciones , PsicometríaRESUMEN
Treatment-free remission (TFR) in chronic myeloid leukemia (CML) is safe under adequate molecular monitoring, but questions remain regarding which factors may be considered predictive for TFR. Argentina Stop Trial (AST) is a multicenter TFR trial showing that 65% of patients sustain molecular remission, and the prior time in deep molecular response (DMR) was associated with successful TFR. Luminex technology was used to characterize cytokines in plasma samples. Using machine learning algorithms, MCP-1 and IL-6 were identified as novel biomarkers and MCP-1low/IL-6low patients showed eightfold higher risk of relapse. These findings support the feasibility of TFR for patients in DMR and MCP-1/IL-6 plasma levels are strong predictive biomarkers.
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Interleucina-6 , Leucemia Mielógena Crónica BCR-ABL Positiva , Humanos , Inhibidores de Proteínas Quinasas , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Biomarcadores , Inducción de Remisión , Resultado del TratamientoRESUMEN
BACKGROUND: Hyperbaric oxygen therapy (HBOT) has been proposed to address COVID-19- associated respiratory failure. However, its biochemical effects are poorly known. METHOD: 50 patients with hypoxemic COVID-19 pneumonia were divided into C group (standard care) and H group (standard care plus HBOT). Blood was obtained at t = 0 and t = 5 days. Oxygen saturation (O2 Sat) was followed up. White blood cell (WC) count, lymphocytes (L) and platelets (P) and serum analysis (glucose, urea, creatinine, sodium, potassium, ferritin, D dimer, LDH and CRP) were carried out. Plasma levels of sVCAM, sICAM, sPselectin, SAA and MPO, and of cytokines (IL-1ß, IL-1RA, IL-6, TNFα, IFNα, IFNγ, IL-15, VEGF, MIP1α, IL-12p70, IL-2 and IP-10) were measured by multiplex assays. Angiotensin Converting Enzyme 2 (ACE-2) levels were determined by ELISA. RESULTS: The average basal O2 Sat was 85 ± 3%. The days needed to reach O2 Sat >90% were: H: 3 ± 1 and C: 5 ± 1 (P < 0,01). At term, H increased WC, L and P counts (all, H vs C: P < 0,01). Also, H diminished D dimer levels (H vs C, P < 0,001) and LDH concentration (H vs C, P < 0.01]. At term, H showed lower levels of sVCAM, sPselectin and SAA than C with respect to basal values (H vs C: ΔsVCAM: P < 0,01; ΔsPselectin: P < 0,05; ΔSAA: P < 0,01). Similarly, H showed diminished levels of TNFα (ΔTNFα: P < 0,05) and increased levels of IL-1RA and VEGF than C respect to basal values (H vs C: ΔIL-1RA and ΔVEGF: P < 0,05). CONCLUSION: Patients underwent HBOT improved O2 Sat with lower levels of severity markers (WC and platelets count, D dimer, LDH, SAA). Moreover, HBOT reduced proinflammatory agents (sVCAM, sPselectin, TNFα) and increased anti-inflammatory and pro-angiogenic ones (IL-1RA and VEGF).
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COVID-19 , Oxigenoterapia Hiperbárica , Insuficiencia Respiratoria , Humanos , SARS-CoV-2 , COVID-19/complicaciones , COVID-19/terapia , Factor de Necrosis Tumoral alfa , Proteína Antagonista del Receptor de Interleucina 1 , Factor A de Crecimiento Endotelial Vascular , Insuficiencia Respiratoria/terapiaRESUMEN
RESUMEN Introducción: Los trastornos intraventriculares de la conducción constituyen una manifestación habitual en los pacientes con enfermedad de Chagas con función ventricular izquierda conservada. Se desconoce si su presencia puede estar asociada a una mayor actividad inflamatoria. Objetivos: Determinar si existe una correlación entre los niveles de interleuquinas y la presencia de trastornos intraventriculares de la conducción en pacientes con serología positiva para enfermedad de Chagas y fracción de eyección ventricular izquierda conservada. Material y métodos: Se evaluó a 22 pacientes con edades comprendidas entre 21 y 80 años, seropositivos para enfermedad de Chagas, de más de 20 años de evolución y fracción de eyección ventricular izquierda mayor del 50%. Se analizó, además, un grupo control de 14 individuos sanos. Se determinaron las concentraciones en plasma de IFN-γ, IL-1β, IL-6, IL-10, IL-12 (p70), IL-15, IL-17A, MCP-1/CCL2, MIP-1 a/CCL3, TNF-a e IL-2. Se consideró trastornos intraventriculares de la conducción a la presencia de bloqueo de rama derecha, hemibloqueo anterior izquierdo o bloqueo de rama izquierda. Resultados: De los 22 pacientes con serología positiva para enfermedad de Chagas, 10 presentaron trastornos de la intraventriculares de la conducción (45,4%). En el grupo con trastornos intraventriculares de la conducción, se observaron niveles elevados de interleuquinas de alto efecto inflamatorio como INF-γ, IL-15, IL-2 (p70), IL-12, MP1-a, en comparación al grupo control, además de presentar altos valores de IL-10 como mecanismo modulador de una respuesta inmunitaria excesiva. Conclusiones: La asociación entre niveles elevados de interleuquinas y la presencia de trastornos intraventriculares de la conducción plantea un posible proceso inflamatorio crónico para su desarrollo en pacientes chagásicos con fracción de eyección ventricular izquierda conservada.
ABSTRACT Background: Intraventricular conduction disturbances are common in patients with Chagas disease and preserved left ventricular ejection fraction, but their association with higher inflammatory activity is unknown. Objectives: The aim of this study was to determine the presence of an association between interleukin levels and intraventricular conduction disturbances in patients with positive serology for Chagas disease and preserved left ventricular function. Methods: Twenty-two patients between 22 and 80 years of age with positive serology test for Chagas disease with more than 20 years progression and left ventricular ejection fraction ≥50% were included in the study and compared with a control group of 14 healthy individuals. Plasma levels of IFN-γ, IL-1β, IL-6, IL-10, IL-12 (p70), IL-15, IL-17A, MCP-1/CCL2, MIP-1 a/CCL3, TNF-a and IL-2 were measured in patients and controls. Right bundle branch block, left anterior hemiblock or left bundle branch block were considered intraventricular conduction disturbances. Results: Among the 22 patients with positive serology for Chagas disease, 10 presented intraventricular conduction disturbances (45.4%). This group had elevated levels of interleukins with high inflammatory effect such as INF-γ, IL-15, IL-2, IL-12, MIP-1 a, compared with the control group, and high levels of IL-10 as a regulatory mechanism of an excessive immune response. Conclusions: The association between elevated levels of inflammatory interleukins and intraventricular conduction disturbances suggests that chronic inflammation may play a role in the development of these abnormalities in patients with positive serology for Chagas disease and preserved left ventricular ejection function.
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Foot-and mouth disease (FMD) is an animal disease that generates many economic impacts and sanctions on the international market. In 2018, Brazil, the world's largest beef exporter, had the recognition by World Organization for Animal Health (OIE) as a country free of FMD with vaccination and proposed to withdraw FMD vaccination throughout the country, based on a 10-year schedule, beginning in 2019. Therefore, Brazil needs studies to help the decision-making process, particularly regarding the availability of resources for strengthening of official animal health services. The state of Mato Grosso do Sul (MS) was chosen to be analyzed for three reasons: the size of its herd, the economic importance of its livestock and its location-which lies on the border with Paraguay and Bolivia. The current study adopted the Social Network Analysis and performed an exploratory analysis of cattle movement in MS. The most central municipalities in the networks were identified and they can be seen as crucial in strategies to monitor animal movement and to control outbreaks. The cattle movement networks demonstrated to be strongly connected, implying a high-speed potential FMD diffusion, in case of reintroduction. In a second stage, we performed an exploratory analysis of animal movement within the state, assuming distinct points in time for the identification of animal origin. The results of the analysis underlined the need and relevance of investing in animal control, sanitary education for producers and equipment and technologies to assist in the early detection, diagnosis, and eradication of outbreaks in a fast and efficient manner, preventing a possible outbreak from spreading to other regions.
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BACKGROUND: Microalgal triglyceride (TAG) synthesis has attracted considerable attention. Particular emphasis has been put towards characterizing the algal homologs of the canonical rate-limiting enzymes, diacylglycerol acyltransferase (DGAT) and phospholipid:diacylglycerol acyltransferase (PDAT). Less work has been done to analyze homologs from a phylogenetic perspective. In this work, we used HMMER iterative profiling and phylogenetic and functional analyses to determine the number and sequence characteristics of algal DGAT and PDAT, as well as related sequences that constitute their corresponding superfamilies. We included most algae with available genomes, as well as representative eukaryotic and prokaryotic species. RESULTS: Amongst our main findings, we identified a novel clade of DGAT1-like proteins exclusive to red algae and glaucophyta and a previously uncharacterized subclade of DGAT2 proteins with an unusual number of transmembrane segments. Our analysis also revealed the existence of a novel DGAT exclusive to green algae with moderate similarity to plant soluble DGAT3. The DGAT3 clade shares a most recent ancestor with a group of uncharacterized proteins from cyanobacteria. Subcellular targeting prediction suggests that most green algal DGAT3 proteins are imported to the chloroplast, evidencing that the green algal chloroplast might have a soluble pathway for the de novo synthesis of TAGs. Heterologous expression of C. reinhardtii DGAT3 produces an increase in the accumulation of TAG, as evidenced by thin layer chromatography. CONCLUSIONS: Our analysis contributes to advance in the knowledge of complex superfamilies involved in lipid metabolism and provides clues to possible enzymatic players of chloroplast TAG synthesis.
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Chlorophyta/metabolismo , Cloroplastos/metabolismo , Diacilglicerol O-Acetiltransferasa/metabolismo , Redes y Vías Metabólicas , Triglicéridos/metabolismo , Secuencias de Aminoácidos , Secuencia de Aminoácidos , Chlorophyta/clasificación , Chlorophyta/genética , Cloroplastos/genética , Biología Computacional/métodos , Simulación por Computador , Secuencia Conservada , Diacilglicerol O-Acetiltransferasa/química , Diacilglicerol O-Acetiltransferasa/genética , Evolución Molecular , Ferredoxinas/química , Ferredoxinas/genética , Ferredoxinas/metabolismo , Redes y Vías Metabólicas/ética , Filogenia , Posición Específica de Matrices de Puntuación , Triglicéridos/biosíntesisRESUMEN
PROBLEM: Multiparity increased the number of trophoblast cells in decidua of both low and high fetal loss mouse models. However, they differ in fetal survival rate and maternal thymocyte subpopulations, suggesting that trophoblast invasiveness is not equivalent. Our aim was to explore the involved mechanism. METHOD OF STUDY: We studied placentae from primiparous and multiparous females of low and high fetal loss models. We investigated invasiveness in vitro, expression of plasminogen, and its activators: tissue type (tPA)-urokinase type (uPA), and activity and expression of matrix metalloproteinases (MMP)-2 and MMP-9. RESULTS: Placental invasiveness is upregulated by multiparity, but lesser in the high fetal loss model. Multiparous animals showed elevated expression of plasminogen and uPA. However, the high fetal loss combination showed higher expression of a short and less active fragment of uPA (LMW-uPA). MMP-2, MMP-9, and tPA were unaffected. CONCLUSION: uPA would participate in the increased multiparity-associated placental invasiveness.
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Paridad/fisiología , Placenta/metabolismo , Placentación/fisiología , Plasminógeno/biosíntesis , Activador de Plasminógeno de Tipo Uroquinasa/biosíntesis , Animales , Western Blotting , Femenino , Inmunohistoquímica , Ratones , Modelos Animales , Embarazo , Trofoblastos/metabolismo , Regulación hacia ArribaRESUMEN
Pheromone-baited traps have been widely used in integrated pest management programs, but their economic value for growers has never been reported. We analyzed the economic benefits of long-term use of traps baited with the citrus fruit borer Gymnandrosoma aurantianum sex pheromone in Central-Southern Brazil. Our analysis show that from 2001 to 2013 citrus growers avoided accumulated pest losses of 132.7 million to 1.32 billion USD in gross revenues, considering potential crop losses in the range of 5 to 50%. The area analyzed, 56,600 to 79,100 hectares of citrus (20.4 to 29.4 million trees), corresponds to 9.7 to 13.5% of the total area planted with citrus in the state of São Paulo. The data show a benefit-to-cost ratio of US$ 2,655 to US$ 26,548 per dollar spent on research with estimated yield loss prevented in the range of 5-50%, respectively. This study demonstrates that, in addition to the priceless benefits for the environment, sex pheromones are invaluable tools for growers as their use for monitoring populations allows rational and reduced use of insecticides, a win-win situation.
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A new, fast, automated and inexpensive sample pre-treatment method for (99)Tc determination by inductively coupled plasma-mass spectrometry (ICP-MS) detection is presented. The miniaturized approach is based on a lab-on-valve (LOV) system, allowing automatic separation and preconcentration of (99)Tc. Selectivity is provided by the solid phase extraction system used (TEVA resin) which retains selectively pertechnetate ion in diluted nitric acid solution. The proposed system has some advantages such as minimization of sample handling, reduction of reagents volume, improvement of intermediate precision and sample throughput, offering a significant decrease of both time and cost per analysis in comparison to other flow techniques and batch methods. The proposed LOV system has been successfully applied to different samples of environmental interest (water and soil) with satisfactory recoveries, between 94% and 98%. The detection limit (LOD) of the developed method is 0.005 ng. The high durability of the resin and its low amount (32 mg), its good intermediate precision (RSD 3.8%) and repeatability (RSD 2%) and its high extraction frequency (up to 5 h(-1)) makes this method an inexpensive, high precision and fast tool for monitoring (99)Tc in environmental samples.
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Monitoreo del Ambiente/instrumentación , Contaminantes Radiactivos/aislamiento & purificación , Suelo/química , Extracción en Fase Sólida/instrumentación , Tecnecio/aislamiento & purificación , Agua/análisis , Monitoreo del Ambiente/economía , Diseño de Equipo , Análisis de Inyección de Flujo/economía , Análisis de Inyección de Flujo/instrumentación , Límite de Detección , Espectrometría de Masas/economía , Espectrometría de Masas/instrumentación , Contaminantes Radiactivos/análisis , Extracción en Fase Sólida/economía , Tecnecio/análisisRESUMEN
UDP-Glucose:glycoprotein glucosyltransferase (UGGT) is a central component of the endoplasmic reticulum (ER) glycoprotein-folding quality control system, which prevents the exit of partially folded species. UGGT activity can be regulated by the accumulation of misfolded proteins in the ER, a stimulus that triggers a complex signaling pathway known as unfolded protein response (UPR) which is closely associated with inflammation and disease. In this work, we investigated the effect of progesterone (P4) on the expression and activity of UGGT in a mouse hybridoma. We detected the expression of two UGGT isoforms, UGGT1 and UGGT2, and demonstrated that both isoforms are active in these cells. Interestingly, the expression of each isoform is regulated by high physiological P4 concentrations. This work provides the first evidence of a hormonal regulation of UGGT isoform expression and activity, which might influence the glycoprotein quality control mechanism. These findings could contribute to the study of pathologies triggered by the accumulation of misfolded proteins.
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Glicoproteínas/química , Glicoproteínas/metabolismo , Hexosiltransferasas/metabolismo , Progesterona/farmacología , Pliegue de Proteína , Animales , Silenciador del Gen/efectos de los fármacos , Glucosiltransferasas , Isoenzimas/metabolismo , Ratones , ARN Interferente Pequeño/metabolismoRESUMEN
It has been reported that fetal lymphoid progenitor cells are acquired during gestation and are able to develop in the maternal mouse thymus into functional T cells. Moreover, previous pregnancies increase the number of fetal cells in the mother. In the present study, we investigated whether mouse pregnancy induces changes in T lymphocyte subsets in the maternal thymus. We determined the T lymphocyte subsets in two allogeneic cross-breedings, namely CBA/J×BALB/c (normal) and CBA/J×DBA/2 (abortion prone), and investigated the effects of the age and parity of the female, as well as pregnancy outcome, on thymocyte populations. In addition, hormonal effects were evaluated in a syngeneic combination (CBA/J×CBA/J). We found that during pregnancy both hormonal and allogeneic stimuli induced a reduction in the CD4(+)CD8(+) subset with an increase in the CD4(+)CD8(-) population. Only young females of the normal combination exhibited an increase in the CD4(-)CD8(+) population. All young mice showed an increase in CD4(+)CD25(+)FoxP3(+) T cells. Interestingly, the γδT thymus pool was increased in all females of the normal allogeneic pregnancy only, suggesting the participation of this pool in the observed beneficial effect of multiparity in this cross-breeding. Our results demonstrate that allogeneic pregnancies induce important variations in maternal thymocyte subpopulations depending on the age of the female and the male component of the cross-breeding.
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Hibridación Genética/inmunología , Ratones Endogámicos BALB C/inmunología , Ratones Endogámicos CBA/inmunología , Subgrupos de Linfocitos T , Timo/citología , Aborto Veterinario/genética , Envejecimiento , Animales , Femenino , Reabsorción del Feto/veterinaria , Edad Gestacional , Tamaño de la Camada , Ratones , Paridad , EmbarazoRESUMEN
Mercury is considered one of the most toxic elements for plants and animals. Nevertheless, in the Middle East, Asia and Latin America, whitening creams containing mercury are being manufactured and purchased, despite their obvious health risks. Due to the mass distribution of these products, this can be considered a global public health issue. In Mexico, these products are widely available in pharmacies, beauty aid and health stores. They are used for their skin lightening effects. The aim of this work was to analyze the mercury content in some cosmetic whitening creams using the cold vapor technique coupled with atomic absorption spectrometry (CV-AAS). A total of 16 skin-lightening creams from the local market were investigated. No warning information was noted on the packaging. In 10 of the samples, no mercury was detected. The mercury content in six of the samples varied between 878 and 36,000 ppm, despite the fact that the U.S. Food and Drug Administration (FDA) has determined that the limit for mercury in creams should be less than 1 ppm. Skin creams containing mercury are still available and commonly used in Mexico and many developing countries, and their contents are poorly controlled.
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Cosméticos/análisis , Mercurio/aislamiento & purificación , Piel , México , Espectrofotometría AtómicaRESUMEN
The presence of additional N-glycans in the Fab region of IgG has shown to dramatically modify the properties and functionality of these molecules including changes in antibody affinity and stability. However, the underlying molecular mechanism responsible for the presence or absence of these glycans remains unknown. Polypeptide N-linked glycosylation is catalyzed in the lumen of the endoplasmic reticulum by the oligosaccharyltransferase complex. Mammalian cells can express two isoforms of the oligosaccharyltransferase catalytic subunit (STT3-A and STT3-B), which are endowed with distinct enzymatic properties. In this work we employed a murine hybridoma cell culture to study whether the expression of STT3 isoforms could be modulated by progesterone, thus altering the pattern of IgG N-glycosylation. We found that progesterone induces a switch of STT3 isoform expression, increasing IgG N-glycosylation. These effects were dependent on the progesterone-induced blocking factor (PIBF), whose concentration was modulated by progesterone. PIBF was previously found to be an immunomodulatory molecule relevant for the maintenance of pregnancy. We concluded that the STT3-B/STT3-A ratio modulates the N-glycosylation level of IgG, in agreement with previous data showing that full N-glycosylation of polypeptides requires cooperation between both catalytic isoforms. This work provides the first evidence that STT3 isoforms can be hormonally modulated, with marked consequences on IgG N-glycosylation.
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Hexosiltransferasas/metabolismo , Inmunoglobulina G/metabolismo , Proteínas de la Membrana/metabolismo , Proteínas Gestacionales/metabolismo , Progesterona/farmacología , Isoformas de Proteínas/metabolismo , Animales , Anticuerpos Bloqueadores/farmacología , Dinitrofenoles/inmunología , Regulación de la Expresión Génica/inmunología , Glicosilación/efectos de los fármacos , Hibridomas , Inmunomodulación , Ratones , Proteínas Gestacionales/inmunologíaRESUMEN
OBJETIVO: Descrever e comparar os métodos de imagem e os aspectos clínicos em quatro recém-natos a termo diagnosticados como trombose venosa cerebral, sem dano encefálico, adscritos a uma unidade de terapia intensiva neonatal. MATERIAIS E MÉTODOS: Revisão em 10 anos com quatro casos diagnosticados como trombose venosa cerebral por meio de ultrassonografia transfontanela com Doppler e confirmados por ressonância magnética/angiorressonância, correlacionados aos aspectos clínicos e evolução neurológica. RESULTADOS: A ultrassonografia foi normal em 75 por cento dos casos e a ressonância magnética, em 100 por cento. No caso alterado, a dilatação venosa foi identificada. O Doppler e a angiorressonância estavam alterados em 100 por cento dos casos. Dos aspectos clínicos, a hipóxia (100 por cento) e a convulsão precoce (100 por cento) predominaram, com potencial evocado alterado em 50 por cento dos casos. Na avaliação do neurodesenvolvimento, todas as áreas estiveram dentro da normalidade até a última avaliação. CONCLUSÃO: A ultrassonografia associada ao Doppler é capaz de identificar as alterações da trombose venosa cerebral, devendo ser complementada com a ressonância magnética, que é o padrão ouro de diagnóstico.
OBJECTIVE: To describe and compare imaging methods and clinical findings of cerebral venous thrombosis in four full-term neonates without brain damage, admitted to a neonatal intensive care unit. MATERIALS AND METHODS: Ten-year review of four cases diagnosed with cerebral venous thrombosis by transfontanellar ultrasonography associated with Doppler fluxometry and confirmed by magnetic resonance imaging/magnetic resonance angiography in correlation with clinical findings and neurological progression. RESULTS: Ultrasonography presented normal results in 75 percent of cases and magnetic resonance imaging in 100 percent. Doppler fluxometry and magnetic resonance angiography were abnormal in 100 percent of cases. Hypoxia (100 percent) and early seizures (100 percent) were predominant among clinical findings with evoked potential changes in 50 percent of cases. In the assessment of the neurodevelopment all the areas remained within normality parameters up to the conclusion of the present study. CONCLUSION: Ultrasonography in association with Doppler can identify changes related to cerebral venous thrombosis and should be complemented with magnetic resonance imaging that is the gold standard for diagnosis in these cases.
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Humanos , Masculino , Recién Nacido , Hipoxia/congénito , Neurología , Sepsis/congénito , Trombosis Intracraneal/diagnóstico , Imagen por Resonancia Magnética , Espectroscopía de Resonancia Magnética , Ultrasonografía Doppler/métodosRESUMEN
To analyze immunomodulating effects related to parity status, we studied trophoblast invasion grade, placental expression and systemic concentration of VEGF and its receptor Flt-1 in normal fertile (CBA/JxBALB/c) mice and abortion-prone (CBA/JxDBA/2) H-2(d)xH-2(k) mice. BALB/c or DBA/2 mated CBA/J females were, respectively, divided into the following groups: primiparous young (3.0+/-0.5 months old); primiparous old (8.5+/-0.5 months old) and multiparous old (8.5+/-0.5 months old, with 4 pregnancies). Immunohistochemical analysis of term placentae from both multiparous groups revealed various layers of invasive trophoblast tissue, identified as cytokeratin+/vimentin- cells, in contrast to the single layer detected in the placentae of primiparous animals, indicating that multiparity increases trophoblast invasion regardless of the success of the pregnancy outcome. Invasive trophoblast tissue from primiparous CBA/JxDBA/2 placentae showed diminished VEGF expression in comparison with the normal fertile group, while both multiparous groups demonstrated high expression of VEGF in the invasive trophoblast tissue. Placental expression of Flt-1 was similar in all groups. However, the primiparous CBA/JxBALB/c group showed the highest plasma concentration of sFlt-1 at term, while both multiparous groups demonstrated low circulating levels. No differences in circulating VEGF levels were observed among the groups. These results demonstrate an increase in trophoblast invasion tissue and expression of VEGF in the maternal-fetal interface in multiparous mice compared to primiparous mice. Moreover, the placenta appears to be able to regulate the circulating levels of VEGF by releasing sFlt-1.
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Aborto Espontáneo/fisiopatología , Intercambio Materno-Fetal , Paridad , Trofoblastos/metabolismo , Factor A de Crecimiento Endotelial Vascular/biosíntesis , Receptor 1 de Factores de Crecimiento Endotelial Vascular/biosíntesis , Aborto Espontáneo/sangre , Aborto Espontáneo/genética , Aborto Espontáneo/metabolismo , Animales , Proliferación Celular , Femenino , Regulación del Desarrollo de la Expresión Génica , Masculino , Intercambio Materno-Fetal/fisiología , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos CBA , Ratones Endogámicos DBA , Paridad/fisiología , Embarazo , Trofoblastos/patología , Factor A de Crecimiento Endotelial Vascular/genética , Receptor 1 de Factores de Crecimiento Endotelial Vascular/sangre , Receptor 1 de Factores de Crecimiento Endotelial Vascular/genéticaRESUMEN
Estudo retrospectivo de dois casos de hemorragia craniana de localização atípica em 777 recém-natos internados na unidade de terapia intensiva neonatal da Casa de Saúde São José, Rio de Janeiro, RJ. Foram avaliados os aspectos clínicos e o diagnóstico por métodos de imagem. Verificamos que a ultrassonografia foi diagnóstica nos dois casos quando comparada com a ressonância magnética. Em relação à etiologia, esta foi multifatorial, e a manifestação clínica silenciosa independente da localização. Até o presente momento, a avaliação neurológica tem tido curso satisfatório, embora os pacientes ainda tenham baixa idade para a avaliação neurológica definitiva.
Retrospective study of two cases of atypically localized cerebral hemorrhage among 777 newborns admitted to the neonatal intensive care unit at Casa de Saúde São José, Rio de Janeiro, RJ, Brazil. Clinical findings and imaging diagnoses were evaluated. The diagnostic effectiveness of ultrasonography was established by correlation with magnetic resonance imaging findings. Multifactorial etiology was observed, besides silent clinical presentation independently from localization. So far the neurological evaluation has satisfactorily progressed although the patients are still too young to allow a definite neurological evaluation.
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Humanos , Masculino , Femenino , Recién Nacido , Trastornos Cerebrovasculares , Cerebro/anomalías , Hemorragia Cerebral/diagnóstico , Hemorragia Cerebral/etiología , Hemorragias Intracraneales , Hemorragias Intracraneales , Brasil , Imagen por Resonancia Magnética , Estudios RetrospectivosRESUMEN
Pregnancy induces collagen-induced arthritis (CIA) remission in rats. Placental hormones, cytokines and growth factors can regulate immune cell activity at the feto-maternal interface as well as at the systemic level. We assessed the effect of placental culture supernatants (PS) in CIA developed in rats after the inoculation of collagen type II (CII) in complete Freund's adjuvant. After the onset of CIA, animals were injected by ip route with seven doses of PS. On the 18th day of treatment with PS, serum anti-CII antibody (total IgG, IgG(1), IgG(2a), IgG(2b), IgG asymmetric molecules) and cytokine levels were determined by ELISA. An arthritic index was used by daily measure of joint swelling and visual signs of arthritis. Our results demonstrated that the PS treatment diminished CIA symptoms, reduced TNF-alpha, INF-gamma and anti-CII antibody serum levels, increased the proportion of asymmetric IgG anti-CII antibodies and affected IgG(1)/IgG(2a) and IgG(1)/IgG(2b) ratio. Two weeks after the last PS inoculation there was a recurrence of arthritis, a rise in IgG anti-CII and, simultaneously, the percentage of asymmetric IgG anti-CII fell. We concluded that PS have an effective CIA suppressor activity partly due to the modulation of humoral immune response and may be closely related to an inhibitory effect on TNF-alpha and INF-gamma production.
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Formación de Anticuerpos/inmunología , Artritis Experimental/inmunología , Colágeno Tipo II/inmunología , Inmunoglobulina G/sangre , Placenta/metabolismo , Animales , Anticuerpos/inmunología , Formación de Anticuerpos/efectos de los fármacos , Artritis Experimental/sangre , Artritis Experimental/fisiopatología , Artritis Experimental/terapia , Técnicas de Cultivo de Célula , Células Cultivadas , Colágeno Tipo II/administración & dosificación , Medios de Cultivo Condicionados/farmacología , Citocinas/antagonistas & inhibidores , Citocinas/metabolismo , Femenino , Inmunoglobulina G/inmunología , Embarazo , Ratas , Ratas Wistar , Índice de Severidad de la EnfermedadRESUMEN
Asymmetric IgG antibodies behave as antigen-blocking due to the presence of a mannose-rich oligosaccharide residue in one of the Fab fragments of the molecule. This feature prevents the interaction of this antibody with the antigenic epitope, then they are unable to activate of the immune effector mechanisms. Taking into account that macrophages modulate the adaptive immune response according to the nature of the stimulating antigen and that IL-6 increases the synthesis of asymmetric IgG, in this work we analysed the differential modulation of the synthesis of asymmetric IgG by culture supernatants from peritoneal macrophages (CSPM) stimulated with either OVA-polystyrene beads or soluble OVA. The levels of IL-10, IL-6 and TNFalpha were determined in CSPM to find elevated levels of IL-6 and TNFalpha only in those cultures stimulated with OVA-coated polystyrene beads. The 112D5 hybridoma was cultured in the presence of CSPM from cells stimulated with OVA-polystyrene beads or soluble OVA. There was an increase in the synthesis of asymmetric IgG only in those cultures of the hybridoma treated with CSPM stimulated with OVA-polystyrene beads this CSPM also had an antiproliferative effect on the hybridoma. A neutralizing anti-IL-6 antibody inhibited the synthesis of asymmetric IgG but could not revert the effect of such CSPM on the viability of the hybridoma. In addition, our results demonstrated that the murine TNFalpha, at a concentration similar to that found in the particle-stimulated CSPM, had an inhibitory effect on cell growth. In summary, IL-6 and TNFalpha are secreted at different concentrations by peritoneal macrophages depending upon the physicochemical nature of the stimulus, thus conditioning the humoral immune response elicited. The IL-6 present in the CSPM can regulate the secretion of asymmetric IgG and, together with TNFalpha can also regulate cell proliferation. Results obtained in this work would contribute to the knowledge of the role of macrophages in the modulation of the quality of the humoral immune response generated upon stimulation with particulate antigens.
Asunto(s)
Inmunoglobulina G/biosíntesis , Macrófagos Peritoneales/fisiología , Animales , Proliferación Celular , Células Cultivadas , Femenino , Hibridomas/inmunología , Interleucina-10/metabolismo , Interleucina-6/metabolismo , Macrófagos Peritoneales/inmunología , Macrófagos Peritoneales/metabolismo , Ratones , Ratones Endogámicos BALB C , Ovalbúmina/inmunología , Poliestirenos/inmunología , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
PROBLEM: Multiparity status has been found to bring beneficial effects both to the maintenance of pregnancy and to the offspring; however, these effects have not been fully explained. We have previously reported that placentae obtained from multiparous females belonging to a syngeneic mouse crossbreeding showed an important increase in the number of placental macrophages, suggesting that they might constitute a protective subpopulation. Taking into account that macrophage-colony stimulating factor (M-CSF) and granulocyte-colony stimulating factor (G-CSF) have proved to modulate macrophage activity and that both factors and/or their receptors have been found at feto-maternal interface, in this paper we analyzed the presence of M-CSF and G-CSF in placental tissue employing the same multiparity mouse model in order to investigate the influence of parity status on local immunoregulation factors of macrophage activity. METHOD OF STUDY: Three groups of mice (CBA/J x CBA/J) were analyzed: Primiparous Young, 3.0 +/- 0.5 months old (PY); Primiparous Old, 8.5 +/- 0.5 months old (PO) and Multiparous Old, 8.5 +/- 0.5 months old, with three to four previous pregnancies (MO). The presence of M-CSF and G-CSF in placental tissue was analyzed by immunohistochemistry. Cytokeratin (CK) and vimentin (VIM) expression and PAS staining were also studied. RESULTS: The three groups showed a similar immunostaining pattern for M-CSF in the whole placental trophoblast, while the expression of G-CSF was significantly higher only in the spongy zone in the MO group. Furthermore, all the MO placentae showed 5-11 layers of cells adjacent to the decidua, where G-CSF and M-CSF were highly detected. Conversely, they constituted a thin layer in PY and PO placentae. These cells were proved to be CK(+) and VIM(-) thus demonstrating their trophoblast origin. In addition, the layers closer to the decidua were also PAS+ suggesting that they could be interstitial cells, a type of invading trophoblast. CONCLUSIONS: In our mouse model, we observed an increase in the expression of G-CSF in placental spongiotrophoblast cells in multiparous females, which have been previously proposed as progenitors of the interstitial cells. Furthermore, this is the first report that indicates that parity status increases trophoblast invasion inducing a proliferative effect of the invading cells on the maternal tissue. We suggest that M-CSF and G-CSF secreted by these invading cells could favor the recruitment of macrophages to the trophoblast and might modulate their activity inducing a switch to a protective, non-inflammatory population.
Asunto(s)
Factor Estimulante de Colonias de Granulocitos/biosíntesis , Factor Estimulante de Colonias de Macrófagos/biosíntesis , Paridad/fisiología , Placenta/metabolismo , Embarazo/fisiología , Animales , Femenino , Inmunohistoquímica/métodos , Intercambio Materno-Fetal/fisiología , Ratones , Placenta/citologíaRESUMEN
Durante una respuesta inmune ocurren cambios en la cantidad y calidad de los anticuerpos que se sintetizan. En el presente trabajo se describen las propiedades fisicoquímicas y el comportamiento biológico de los anticuerpos asimétricos, así como su funcionamiento beneficioso o perjudicial para el huésped, de acuerdo con la naturaleza del antígeno y la situación particular en la que actúan. Estos anticuerpos son de la clase IgG, actúan como bloqueantes, univalentes, incapaces de formar complejos adecuados para la activación de los mecanismos biológicos que llevan al daño del agente agresor. Tienen dos paratopes, uno de los cuales es de muy baja afinidad para el antígeno, lo que es consecuencia de un impedimento estérico originado por un hidrato de carbono del tipo high mannose, que determina la asimetría funcional, haciendo que se comporten como univalentes. Cuando los anticuerpos asimétricos tienen especificidad para antígenos propios son beneficiosos para el huésped, participando en los mecanismos de la tolerancia, siendo perjudiciales cuando los antígenos son extraños, como ocurre en las infecciones microbianas crónicas. Los anticuerpos asimétricos cumplen una función beneficiosa durante la preñez, no obstante de que los antígenos fetales de origen paterno, responsables del proceso son extraños para el huésped. La placenta secreta factores (moléculas) que regulan la síntesis de éstos anticuerpos, favoreciendo por éste mecanismo la sobrevida del feto en el útero materno. Finalmente, en el trabajo se describen métodos para detección y dosaje de anticuerpos bloqueantes así como ejemplos para la interpretación de los resultados obtenidos (AU)