The Antitumoral Effect In Ovo of a New Inclusion Complex from Dimethoxycurcumin with Magnesium and Beta-Cyclodextrin.

Breast cancer is one of the leading causes of death in the female population because of the resistance of cancer cells to many anticancer drugs used. Curcumin has cytotoxic activities against breast cancer cells, although it has limited use due to its poor bioavailability and rapid metabolic elimination. The synthesis of metal complexes of curcumin and curcuminoids is a relevant topic in the search for more active and selective derivatives of these molecular scaffolds. However, solubility and bioavailability are concomitant disadvantages of these types of molecules. To overcome such drawbacks, the preparation of inclusion complexes offers a chemical and pharmacologically safe option for improving the aqueous solubility of organic molecules. Herein, we describe the preparation of the inclusion complex of dimethoxycurcumin magnesium complex (DiMeOC-Mg, (4)) with beta-cyclodextrin (DiMeOC-Mg-BCD, (5)) in the stoichiometric relationship 1:1. This new inclusion complex's solubility in aqueous media phosphate buffer saline (PBS) was improved by a factor of 6x over the free metal complex (4). Furthermore, 5 affects cell metabolic rate, cell morphology, cell migration, induced apoptosis, and downregulation of the matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9), interleukin-6 (IL-6), and signal transducer and activator of transcription-3 (STAT3) expression levels on MD Anderson metastasis breast-231 cancer (MDA-MB-231) cell lines. Results of an antitumor assay in an in ovo model showed up to 30% inhibition of tumor growth for breast cancer (MDA-MB-231) when using (5) (0.650 mg/kg dose) and 17.29% inhibition with the free homoleptic metal complex (1.5 mg/kg dose, (4)). While the formulation of inclusion complexes from metal complexes of curcuminoids demonstrates its usefulness in improving the solubility and bioavailability of these metallodrugs, the new compound (5) exhibits excellent potential for use as a therapeutic agent in the battle against breast cancer.

First Gallium and Indium Crystal Structures of Curcuminoid Homoleptic Complexes: All-Different Ligand Stereochemistry and Cytotoxic Potential.

The crystal structure determination of metal complexes of curcuminoids is a relevant topic to assess their unequivocal molecular structure. We report herein the first two X-ray crystal structures of homoleptic metal complexes of a curcuminoid, namely Dimethoxycurcumin (DiMeOC), with gallium and indium. Such successful achievement can be attributed to the suppression of interactions from the phenolic groups, which favor an appropriate molecular setup, rendering Dimethoxycurcumin gallium ((DiMeOC)2-Ga) and Dimethoxycurcumin indium ((DiMeOC)3-In) crystals. Surprisingly, the conformation of ligands in the crystal structures shows differences in each metal complex. Thus, the ligands in the (DiMeOC)2-Ga complex show two different conformers in the two molecules of the asymmetric unit. However, the ligands in the (DiMeOC)3-In complex exhibit three different conformations within the same molecule of the asymmetric unit, constituting the first such case described for an ML3 complex. The cytotoxic activity of the (DiMeOC)2-Ga complex is 4-fold higher than cisplatin against the K562 cell line and has comparable activity towards U251 and PC-3 cell lines. Interestingly, this complex exhibit three times lesser toxicity than cisplatin and even slightly lesser cytotoxicity than curcumin itself.

The Homoleptic Curcumin-Copper Single Crystal (ML2): A Long Awaited Breakthrough in the Field of Curcumin Metal Complexes.

The first single crystal structure of the homoleptic copper (II) ML2 complex (M=Cu (II), L = curcumin) was obtained and its structure was elucidated by X-ray diffraction showing a square planar geometry, also confirmed by EPR. The supramolecular arrangement is supported by C-H···O interactions and the solvent (MeOH) plays an important role in stabilizing the crystal packing Crystallinity was additionally assessed by XRD patterns. The log P value of the complex (2.3 ± 0.15) was determined showing the improvement in water solubility. The cytotoxic activity of the complex against six cancer cell lines substantially surpasses that of curcumin itself, and it is particularly selective against leukemia (K562) and human glioblastoma (U251) cell lines, with similar antioxidant activity to BHT. This constitutes the first crystal structure of pristine curcumin complexed with a metal ion.

Three new coordination geometries of homoleptic Zn complexes of curcuminoids and their high antiproliferative potential.

To our previously reported first crystal structure of a homoleptic zinc curcuminoid complex with square pyramidal geometry, we add herein three new geometries of homoleptic type complexes i.e. octahedral, trigonal-pyramidal, and trigonal-bipyramidal. Octahedral geometry was observed in the new pseudo-polymorph of the DAC-Zn complex resulting from crystallization in DMF, while square-pyramidal geometry was obtained in DMSO. Improving crystallinity involved suppressing the phenolic interactions by etherification and esterification. The complete characterization of these complexes was carried out using SCXRD, IR, MS, EA, liquid, and solid-state NMR. Moreover, the cytotoxic activity of all complexes was evaluated. The IC50 values for the DiMeOC-Zn (7) complex were 8 or 22 times higher than for cisplatin in the U251 and HCT-15 cell lines, indicating a high antiproliferative and therapeutic potential.

Homoleptic Complexes of Heterocyclic Curcuminoids with Mg(II) and Cu(II): First Conformationally Heteroleptic Case, Crystal Structures, and Biological Properties.

We report herein the synthesis and characterization of three heterocyclic curcuminoid ligands and their homoleptic metal complexes with magnesium and copper. Thus, N-methyl-2-pyrrolecarboxaldehyde, Furan-2-carboxaldehyde, and 2-Thiophenecarboxaldehyde were condensed with 2,4-pentanedione-boron trioxide complex. The first N-methyl-2-pyrrole curcuminoid and its Mg(II) complex are reported. All curcuminoid ligands and their corresponding metal complexes were characterized by infrared spectroscopy (IR), liquid state nuclear magnetic resonance (LSNMR), electron paramagnetic resonance (EPR), mass spectrometry (MS) and single crystal X-ray diffraction (SCXRD). The ThiopheneCurc-Cu (9) constitutes the first case of a "conformationally-heteroleptic" complex. The unique six-peaks star arrangement for the ThiopheneCurc ligand derived from the supramolecular description is reported. The metal complexes of FuranCurc-Mg (5) and ThiopheneCurc-Cu (9) have a good antioxidant effect (IC50 = 11.26 ± 1.73 and 10.30 ± 0.59 µM), three and two times higher than their free ligands respectively. Additionally, (5) shows remarkable cytotoxicity against colon cancer adenocarcinoma cell line HCT-15, comparable to that of cisplatin, with a negligible toxic effect in vitro towards a healthy monkey kidney cell line (COS-7).

Seguridad alimentaria y estado nutricional en niños vinculados a centros de desarrollo infantil / Food security and nutritional status in children linked to child development centers in Cordoba, Colombia / Segurança alimentar e estado nutricional em crianças vinculados a centros de desenvolvimento infantil

Resumen Objetivo: determinar la relación entre la seguridad alimentaria y el estado nutricional de niños menores de cinco años que asisten a los Centro de Desarrollo Infantil de Montería, Córdoba, Colombia, 2019. Metodología: estudio correlacional transversal con participación de 388 familias distribuidas en diferentes Centros de Desarrollo Infantil de Montería. A los padres o representantes se les aplicó la encuesta: Escala Latinoamericana y Caribeña de Seguridad Alimentaria, y a los niños se le hizo valoración antropométrica bajo supervisión de adultos responsables. Las variables categóricas fueron medidas, cuya asociación se realizó con la prueba de Chi-cuadrado. Resultados: de las 388 familias, (71,4 %) (n=277) padecían inseguridad alimentaria severa. La valoración antropométrica arrojó que el estado nutricional de los niños menores de cinco años refirió un peso adecuado para la talla (75,1 %), al igual que las niñas (73,9 %), siendo mayor el registro de los varones; con respecto al riesgo por sobrepeso, se encontró un porcentaje mayor en niñas (13.6 %), con relación a los niños (9.1%). La desnutrición aguda severa se encontró en mayor concentración en niñas (2.1 %) frente a los niños (1.0 %). Conclusiones: pese a que la mayor proporción de las familias sufren de inseguridad alimentaria severa, no se encontró nivel de asociación con las variadas formas de malnutrición que padecen algunos de los menores valorados, lo cual podría estar vinculado con la asistencia alimentaria que reciben en los diferentes Centros de Desarrollo Infantil de la ciudad de Montería.

Abstract Objective: To determine the relationship between food security and nutritional status of children under 5 years of age who attend the Child Development Center of Monteria - Córdoba, Colombia, 2019. Methodology: Crosssectional correlational study with the participation of 388 families distributed in different Child Development Centers of Monteria. The Latin American and Caribbean Food Security Scale survey was applied to parents or representatives, and the children underwent anthropometric assessment under supervision of responsible adults. The categorical variables were measured and their association was assessed using the Chi-square test. Results: Of the 388 families (71.4%) (n = 277) suffered from severe food insecurity. Anthropometric assessment showed that the nutritional status of boys under five years of age reported an adequate weight for height (75.1%), as did girls (73.9%), with the record being higher for boys. Regarding the risk of overweight, a higher percentage was found in girls (13.6%) compared to boys (9.1%). Severe acute malnutrition was found in higher concentration in girls (2.1%) compared to boys (1.0%). Conclusions: Despite the fact that the largest proportion of families suffer from severe food insecurity, no association was found with the various forms of malnutrition suffered by some of the children assessed, which could be linked to the food assistance they receive in the different Child Development Centers in the city of Monteria.

Resumo Objetivo: determinar a relação entre a segurança alimentar e o estado nutricional de crianças menores de cinco anos que vão aos Centro de Desenvolvimento Infantil de Montería, Córdoba, Colômbia, 2019. Metodologia: estudo correlacional transversal com participação de 388 famílias distribuídas em diferentes Centros de Desenvolvimento Infantil de Montería. Aos pais ou representantes se lhes aplicou a enquete: Escala Latino-americana e Caribeña de Segurança Alimentar, e às crianças se lhe fez valoração antropométrica baixo supervisão de adultos responsáveis. As variáveis categóricas foram medidas, cuja associação foi feita com o teste de Chi-quadrado. Resultados: das 388 famílias, (71,4 %) (n=277) padeciam insegurança alimentar severa. A valoração antropométrica deu como resultado que o estado nutricional das meninas de cinco anos amostrou um peso adequado para a tamanho (75,1 %), ao igual que as meninas (73,9 %), sendo maior o registro dos homens; com respeito ao risco por sobrepeso, achou-se uma porcentagem maior em meninas (13.6 %), com relação aos meninos (9.1%). A desnutrição aguda severa se encontrou em maior concentração em meninas (2.1 %) frente aos meninos (1.0 %). Conclusões: A pesar de que a maior proporção das famílias sofre de insegurança alimentar severa, não se achou nível de associação com as variadas formas de má nutrição que padecem alguns dos menores valorados, o qual poderia estar vinculado com a assistência alimentar que recebem nos diferentes Centros de Desenvolvimento Infantil da cidade de Montería.

Analisis de Prisma como Metodología para Revisión Sistemática: una Aproximación General

El presente artículo se llevó a cabo en el contexto del programa de doctorado de ciencias de la salud, se llevó a cabo un análisis descriptivo de lo que es una revisión sistemática desde la metodología PRISMA, lo que da lugar a la construcción de nuevos paradigmas metodológicos, para la producción de nuevos saberes en el ámbito de la investigación científica. Inicia con antecedentes de la evolución de la metodología hasta los últimos avances de la misma, etapas principales del desarrollo de la metodología y se anexan los chek list y diagrama de flujo que permiten tomar en consideración para llevar a cabo metodología ítems, destacando las revisiones sistemáticas dentro del programa de doctorado en ciencias de la salud. Se concluye brindando una pequeña justificación del porque la importancia de las revisiones sistemáticas dentro del estudio del sistema de emergencias médica de Nicaragua que permitan tener nuevos paradigmas y fundamentos epistemológicos para la formulación de una propuesta de modelo de sistema de emergencias médicas para Nicaragua y poder mejorar así los indicadores de calidad de la atención prehospitalaria y como apoyo para la toma de decisiones de mejora para las que fueron construidas.

Transnasal Humidified Rapid Insufflation Ventilatory Exchange in Laryngotracheal Resection and Reconstruction: A Report of Two Pregnant Cases.

Introduction: The incidence of tracheal stenosis is progressively increasing. A risk factor for developing this clinical condition is a history of prolonged endotracheal intubation. A transnasal humidified rapid insufflation ventilatory exchange, known as THRIVE, has gained importance in tracheal resection surgeries. Case Presentation: Herein, we describe the anesthetic management of two obstetric patients, a 19-year-old and 29-year-old, with a history of prolonged endotracheal intubation and a diagnosis of tracheal stenosis. The patients required the resection of the tracheal segment and end-to-end anastomosis. The anesthetic management focused on THRIVE using a high-flow nasal cannula. Conclusions: This system proved to be a safe anesthetic technique for pregnant women and the fetus. Furthermore, it allowed surgeons to better visualize the surgical field without the risk of accidental injury to the endotracheal tube.

High Yield Synthesis of Curcumin and Symmetric Curcuminoids: A "Click" and "Unclick" Chemistry Approach.

The worldwide known and employed spice of Asian origin, turmeric, receives significant attention due to its numerous purported medicinal properties. Herein, we report an optimized synthesis of curcumin and symmetric curcuminoids of aromatic (bisdemethoxycurcumin) and heterocyclic type, with yields going from good to excellent using the cyclic difluoro-boronate derivative of acetylacetone prepared by reaction of 2,4-pentanedione with boron trifluoride in THF (ca. 95%). The subsequent cleavage of the BF2 group is of significant importance for achieving a high overall yield in this two-step procedure. Such cleavage occurs by treatment with hydrated alumina (Al2O3) or silica (SiO2) oxides, thus allowing the target heptanoids obtained in high yields as an amorphous powder to be filtered off directly from the reaction media. Furthermore, crystallization instead of chromatographic procedures provides a straightforward purification step. The ease and efficiency with which the present methodology can be applied to synthesizing the title compounds earns the terms "click" and "unclick" applied to describe particularly straightforward, efficient reactions. Furthermore, the methodology offers a simple, versatile, fast, and economical synthetic alternative for the obtention of curcumin (85% yield), bis-demethoxycurcumin (78% yield), and the symmetrical heterocyclic curcuminoids (80-92% yield), in pure form and excellent yields.

Damage control of laryngotracheal trauma: the golden day / Control de daños del trauma laringotraqueal: todo en 24 horas

Abstract Laryngotracheal trauma is rare but potentially life-threatening as it implies a high risk of compromising airway patency. A consensus on damage control management for laryngotracheal trauma is presented in this article. Tracheal injuries require a primary repair. In the setting of massive destruction, the airway patency must be assured, local hemostasis and control measures should be performed, and definitive management must be deferred. On the other hand, management of laryngeal trauma should be conservative, primary repair should be chosen only if minimal disruption, otherwise, management should be delayed. Definitive management must be carried out, if possible, in the first 24 hours by a multidisciplinary team conformed by trauma and emergency surgery, head and neck surgery, otorhinolaryngology, and chest surgery. Conservative management is proposed as the damage control strategy in laryngotracheal trauma.

Resumen El trauma laringotraqueal es poco frecuente, pero con alto riesgo de comprometer la permeabilidad la vía aérea. El presente artículo presenta el consenso de manejo de control de daños del trauma laringotraqueal. En el manejo de las lesiones de tráquea se debe realizar un reparo primario; y en los casos con una destrucción masiva se debe asegurar la vía aérea, realizar hemostasia local, medidas de control y diferir el manejo definitivo. El manejo del trauma laríngeo debe ser conservador y diferir su manejo, a menos que la lesión sea mínima y se puede optar por un reparo primario. El manejo definitivo se debe realizar durante las primeras 24 hora por un equipo multidisciplinario de los servicios de cirugía de trauma y emergencias, cirugía de cabeza y cuello, otorrinolaringología, y cirugía de tórax. Se propone optar por la estrategia de control de daños en el trauma laringotraqueal.

Non-Cytotoxic Dibenzyl and Difluoroborate Curcuminoid Fluorophores Allow Visualization of Nucleus or Cytoplasm in Bioimaging.

Curcumin, the most important secondary metabolite isolated from Curcuma longa, is known for its numerous purported therapeutic properties and as a natural dye. Herein, based on curcumin's intrinsic fluorescence, a search for improved curcumin-based fluorophores was conducted. Within the set of semi-synthetic curcumin derivatives i.e. mono (1), di (2), tri (3), tetra (4) benzylated and dibenzyl-fluoroborate (5), the fluorescence properties of 2 and 5 in solution outstood with a two-fold quantum yield compared to curcumin. Furthermore, all benzylated derivatives showed a favorable minimal cytotoxic activity upon screening at 25 µM against human cancer and non-tumoral COS-7 cell lines, with a reduction of its cytotoxic effect related to the degree of substitution. Fluorophores 2 and 5 are versatile bioimaging tools, as revealed by Confocal Fluorescence Microscopy (CFM), and showed permeation of living cell membranes of astrocytes and astrocytomas. When 2 is excited with a 405- (blue) or 543-nm (green) laser, it is possible to exclusively and intensively visualize the nucleus. However, the fluorescence emission fades as the laser wavelength moves towards the red region. In comparison, 5 allows selective visualization of cytoplasm when a 560-nm laser is used, showing emission in the NIR region, while it is possible to exclusively observe the nucleus at the blue region with a 405-nm laser.

Damage control of laryngotracheal trauma: the golden day.

Laryngotracheal trauma is rare but potentially life-threatening as it implies a high risk of compromising airway patency. A consensus on damage control management for laryngotracheal trauma is presented in this article. Tracheal injuries require a primary repair. In the setting of massive destruction, the airway patency must be assured, local hemostasis and control measures should be performed, and definitive management must be deferred. On the other hand, management of laryngeal trauma should be conservative, primary repair should be chosen only if minimal disruption, otherwise, management should be delayed. Definitive management must be carried out, if possible, in the first 24 hours by a multidisciplinary team conformed by trauma and emergency surgery, head and neck surgery, otorhinolaryngology, and chest surgery. Conservative management is proposed as the damage control strategy in laryngotracheal trauma.

El trauma laringotraqueal es poco frecuente, pero con alto riesgo de comprometer la permeabilidad la vía aérea. El presente artículo presenta el consenso de manejo de control de daños del trauma laringotraqueal. En el manejo de las lesiones de tráquea se debe realizar un reparo primario; y en los casos con una destrucción masiva se debe asegurar la vía aérea, realizar hemostasia local, medidas de control y diferir el manejo definitivo. El manejo del trauma laríngeo debe ser conservador y diferir su manejo, a menos que la lesión sea mínima y se puede optar por un reparo primario. El manejo definitivo se debe realizar durante las primeras 24 hora por un equipo multidisciplinario de los servicios de cirugía de trauma y emergencias, cirugía de cabeza y cuello, otorrinolaringología, y cirugía de tórax. Se propone optar por la estrategia de control de daños en el trauma laringotraqueal.

Diacetylcurcumin: Its Potential Antiarthritic Effect on a Freund's Complete Adjuvant-Induced Murine Model.

The present study aims to evaluate the antiarthritic activity of diacetylcurcumin (DAC), a synthetic derivative where the free phenolic groups of curcumin are derivatized by acetylation, thereby conferring greater lipophilicity to the parent molecule and partially overcoming the limited systemic bioavailability of curcumin. Antiarthritic activity was evaluated on a Freund's complete adjuvant (FCA)-induced murine model of arthritis. Oral administration of DAC (60 and 120 mg/kg) resulted in a significant inhibition of inflammation in the acute and chronic phases, respectively, demonstrating an improved and sustained anti-inflammatory effect, comparable to that of curcumin (150 mg/kg) in the chronic stage at a lower dose. Phenylbutazone (80 mg/kg) was used as a reference drug. The pharmacological consequence of DAC or curcumin treatment is the prevention of secondary lesions commonly associated with this biological model.

Full Structural Characterization of Homoleptic Complexes of Diacetylcurcumin with Mg, Zn, Cu, and Mn: Cisplatin-level Cytotoxicity in Vitro with Minimal Acute Toxicity in Vivo.

At the present time, scientists place a great deal of effort worldwide trying to improve the therapeutic potential of metal complexes of curcumin and curcuminoids. Herein, the synthesis of four homoleptic metal complexes with diacetylcurcumin (DAC), using a ligand designed to prevent the interaction of phenolic groups, rendering metal complexes through the ß-diketone functionality, is reported. Due to their physiological relevance, we used bivalent magnesium, zinc, copper, and manganese for complexation with DAC. The resulting products were characterized by ultraviolet-visible (UV-Vis), fluorescence spectroscopy, infrared spectroscopy (IR), liquid and solid-state nuclear magnetic resonance (NMR), electron paramagnetic resonance (EPR), magnetic moment, mass spectrometry (MS), single crystal, and powder X-ray diffraction (SCXRD and PXRD). Crystallization was achieved in dimethylsulfoxide (DMSO) or N,N-dimethylformamide (DMF) as triclinic systems with space group P-1, showing the metal bound to the ß-diketone function, while the 1H-NMR confirmed the preference of the enolic form of the ligand. Single crystal data demonstrated a 1:2 metal:ligand ratio. The inhibition of lipid peroxidation was evaluated using the thiobarbituric acid reactive substance assay (TBARS). All four metal complexes (Mg, Zn, Cu, and Mn) exhibited good antioxidant effect (IC50 = 2.03 ± 0.27, 1.58 ± 0.07, 1.58 ± 0.15 and 1.24 ± 0.10 µM respectively) compared with butylated hydroxytoluene (BHT) and α-tocopherol. The cytotoxic activity in human cancer cell lines against colon adenocarcinoma (HCT-15), mammary adenocarcinoma (MCF-7), and lung adenocarcinoma (SKLU-1) was found comparable ((DAC)2Mg), or ca. 2-fold higher ((DAC)2Zn) than cisplatin. The acute toxicity assays indicate class 5 toxicity, according to the Organization for Economic Co-operation and Development (OECD) guidelines at doses of 3 g/kg for all complexes. No mortality or changes in the behavior of animals in any of the treated groups was observed. A therapeutic potential can be envisaged from the relevant cytotoxic activity upon human cancer cell lines in vitro and the undetected in vivo acute toxicity of these compounds.

A New Family of Homoleptic Copper Complexes of Curcuminoids: Synthesis, Characterization and Biological Properties.

We report herein the synthesis and crystal structures of five new homoleptic copper complexes of curcuminoids. The scarcity of reports of homoleptic complex structures of curcuminoids is attributed to the lack of crystallinity of such derivatives, and therefore, their characterization by single crystal X-ray diffraction is rare. The ligand design suppressing the phenolic interaction by esterification or etherification has afforded a significant increase in the number of known crystal structures of homoleptic metal complexes of curcuminoids revealing more favorable crystallinity. The crystal structures of the present new copper complexes show four-fold coordination with a square planar geometry. Two polymorphs were found for DiBncOC-Cu when crystallized from DMF. The characterization of these new complexes was carried out using infrared radiation (IR), nuclear magnetic resonance (NMR), electron paramagnetic resonance (EPR), and single crystal X-ray diffraction (SCXRD) and the antioxidant and cytotoxic activity of the obtained complexes was evaluated.

Identificación de levaduras aisladas de exudados vaginales de mujeres que asisten a centros de salud de León, Nicaragua / Identification of yeast clinical isolates in vaginal discharge from women attending public health clinics in León, Nicaragua

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La propuesta de Francisco de Asís, como alternativa de vida ante la crisis de sentido de hoy / Francis assisi’s proposal as a life alternative to the crisis of today’s sense

El presente texto desarrolla elementos de reflexión en torno a los componentes constitutivos de la identidad franciscana, desde el lugar donde son ejercidos los discursos pedagógicos,como una propuesta para la formación de formadores desde la apropiación de valores y principios franciscanos como una propuesta de vida, en medio de un mundo inmerso en una profunda crisis de sentido.

This paper develops elements of reflection on the constituent components of the Franciscan identity, from the place where educational speeches are exercised, as a proposal for the training of trainers from the appropriation of values and Franciscan principles as a proposalof life, in the midst of a world immersed in a profound crisis of sense.

MHC-mismatched mixed chimerism mediates thymic deletion of cross-reactive autoreactive T cells and prevents insulitis in nonobese diabetic mice.

Type 1 diabetic NOD mice have defects in both thymic negative selection and peripheral regulation of autoreactive T cells, and induction of mixed chimerism can effectively reverse these defects. Our recent studies suggest that MHC-mismatched mixed chimerism mediates negative selection of autoreactive thymocytes in wild-type NOD and TCR-transgenic NOD.Rag1(+/+).BDC2.5 mice. However, it remains unknown how mismatched I-A(b) MHC class II can mediate deletion of autoreactive T cells positively selected by I-A(g7). In the present study, we directly tested the hypothesis that mismatched MHC class II in mixed chimeras mediates deletion of cross-reactive autoreactive thymocytes. We first identify that transgenic BDC2.5 T cells from NOD.Rag1(+/+).BDC2.5 but not NOD.Rag1(-/-).BDC2.5 mice possess cross-reactive TCRs with endogenous TCRα-chains; MHC-mismatched H-2(b) but not matched H-2(g7) mixed chimerism mediates thymic deletion of the cross-reactive transgenic T cells in NOD.Rag1(+/+).BDC2.5 mice. Second, by transplanting T cell-depleted (TCD) bone marrow (BM) cells from NOD.Rag1(+/+).BDC2.5 or NOD.Rag1(-/-).BDC2.5 mice into lethally irradiated MHC-mismatched H-2(b) C57BL/6 or MHC-matched congenic B6.H-2(g7) recipients, we demonstrate that NOD.Rag1(+/+).BDC2.5 BM-derived cross-reactive transgenic T cells, but not NOD.Rag1(-/-).BDC2.5 BM-derived non-cross-reactive transgenic T cells, can be positively selected in MHC-mismatched H-2(b) thymus. Third, by cotransplanting NOD.Rag1(+/+).BDC2.5 TCD BM cells with BM cells from MHC-mismatched T cell-deficient C57BL/6 mice into lethally irradiated MHC-matched B6.H-2(g7) recipients, we demonstrate that thymic deletion of the cross-reactive transgenic T cells is dependent on MHC-mismatched donor BM-derived APCs but not on donor BM-derived T cells. Taken together, our studies indicate that MHC-mismatched mixed chimerism can mediate thymic deletion of cross-reactive autoreactive T cells that express more than one TCR.

Osteoma de seios paranasais / Osteoma of paranasal sinuses

Os ossos do crânio poucas vezes são a sede de tumores primários, sendo neles mais comumente encontradas lesões metastaticas...