143 research outputs found
Preoperative evaluation of cytologically indeterminate thyroid nodules with 18F-FDG PET
Esse artigo tem o objetivo de discutir o papel da tomografia por emissão de pósitrons (PET) com 18F-FDG na avaliação pré-operatória de pacientes com nódulos de tireóide com citologia indeterminada. Para o cálculo da sensibilidade, foram selecionados todos os estudos com pacientes com carcinoma de tireóide. Para o cálculo da especificidade, foram selecionados apenas estudos desenhados para avaliação dos pacientes com nódulos com citologia indeterminada. O achado de captação focal na PET-18F-FDG relacionou-se com a presença de carcinoma de tireóide na maioria dos estudos. A sensibilidade do exame foi bastante alta na detecção de malignidade tireoidiana, porém sua especificidade variou de 0% a 66%, sendo de 39% em estudo brasileiro. Concluindo, os estudos indicam que a PET-18F-FDG pode reduzir o número de tireoidectomias desnecessárias em pacientes com nódulos de tireóide com citologia indeterminada. Entretanto, o percentual relativamente elevado de resultados falso-positivos, o alto custo, a baixa disponibilidade do exame em países em desenvolvimento e a pouca experiência clínica ainda limitam o uso da PET-18F-FDG com essa finalidade.The aim of this article is to discuss the role of 18F-FDG Positron Emission Tomography (PET) in the preoperative evaluation of patients with cytologically indeterminate thyroid nodules. All studies with patients with thyroid cancer were selected to the calculation of sensitivity. Only studies aiming to evaluate patients with thyroid nodules whose cytological result was indeterminate were selected to establish the specificity. The finding of focal 18F-FDG uptake at PET was associated with the presence of thyroid malignancy in most of the studies. The sensitivity of the exam to the detection of thyroid malignancy was extremely high, but the specificity varied from 0 to 66%. In our experience, the specificity was 39%. In conclusion, the studies suggest that 18F-FDG PET can reduce the number of unnecessary thyroidectomies performed in patients with cytologically indeterminate thyroid nodules. However, the relatively high percentage of false positive results, the high costs, the low availability of this exam in developing countries and the low clinical experience still restrict the use of 18F-FDG PET when recommended with this aim
Latin American Thyroid Society Recommendations For The Management Of Thyroid Nodules [recomendações Da Sociedade Latino-americana De Tireoide No Manejo De Nódulos Tireoideos]
Several guidelines on diagnosis and treatment of thyroid nodules and cancer have recently been published. However, recommended practices are not always appropriate to different settings or countries. The aim of this consensus was to develop Clinical Guidelines for evaluation and management of patients with thyroid nodules applicable to Latin American countries. The panel was composed by 13 members of the Latin American Thyroid Society involved with research and management of thyroid nodules and cancer from different medical centers in Latin America. The consensus was produced based on the expert opinion of the panel with use of principles of evidence-based medicine. Following a group meeting, a first draft based on the expert opinion of the panel was elaborated and later circulated among panel members for further revision. After revision, this document was submitted to all LATS members for commentaries and considerations and finally revised and refined by the authors. The final recommendations represent state of the art on management of thyroid nodules applied to all Latin American countries. © ABE&M todos os direitos reservados.53911671175Villena, J., Pretell, E., Bocio nodular tóxico en pacientes de zonas yodo deficientes y de la costa (1991) Rev Méd Hered, 2 (4), pp. 149-155Villena, J., Ferrufino, J.C., Klinge, G., Nódulo tireoideo frio. Características clínicas y anatomopatológicas en pacientes migrantes de zonas con deficiencia de yodo y de la costa (1993) Rev Méd Hered, 4 (4), pp. 188-193Harach, H.R., Ceballos, G.A., Thyroid cancer, thyroiditis and dietary iodine: A review based on the Salta, Argentina model (2008) Endocr Pathol, 19 (4), pp. 209-220Pretell, E.A., Delange, F., Hostalek, U., Corigliano, S., Barreda, L., Higa, A.M., Iodine nutrition improves in Latin America (2004) Thyroid, 14 (8), pp. 595-604Harach, H.R., Franssila, K.O., Wasenius, V.M., Occult papillary carcinoma of the thyroid. A "normal" finding in Finland. A systematic autopsy study (1985) Cancer, 56 (3), pp. 531-538Rosai, J., Livolsi, V.A., Sobrinho-Simoes, M., Williams, E.D., Renaming papillary microcarcinoma of the thyroid gland: The Porto proposal (2003) Int J Surg Pathol, 11 (4), pp. 249-251Hay, I.D., Grant, C.S., van Heerden, J.A., Goellner, J.R., Ebersold, J.R., Bergstralh, E.J., Papillary thyroid microcarcinoma: A study of 535 cases observed in a 50-year period (1992) Surgery, 112 (6), pp. 1139-1146Jukkola, A., Bloigu, R., Ebeling, T., Salmela, P., Blanco, G., Prognostic factors in differentiated thyroid carcinomas and their implications for current staging classifications (2004) Endocr Relat Cancer, 11 (3), pp. 571-579Passler, C., Scheuba, C., Prager, G., Kaczirek, K., Kaserer, K., Zettinig, G., Prognostic factors of papillary and follicular thyroid cancer: Differences in an iodine-replete endemic goiter region (2004) Endocr Relat Cancer, 11 (1), pp. 131-139Rossi, R., Roti, E., Trasforini, G., Pansini, G., Cavazzini, L., Zatelli, M.C., Differentiated thyroid cancers 11-20 mm in diameter have clinical and histopathologic characteristics suggesting higher aggressiveness than those ≤ 10 mm (2008) Thyroid, 18 (3), pp. 309-315Curtis, R.E., Rowlings, P.A., Deeg, H.J., Shriner, D.A., Socie, G., Travis, L.B., Solid cancers after bone marrow transplantation (1997) N Engl J Med, 336 (13), pp. 897-904Sippel, R.S., Caron, N.R., Clark, O.H., An evidence-based approach to familial nonmedullary thyroid cancer: Screening, clinical management, and follow-up (2007) World J Surg, 31 (5), pp. 924-933Pacini, F., Pinchera, A., Giani, C., Grasso, L., Doveri, F., Baschieri, L., Serum thyroglobulin in thyroid carcinoma and other thyroid disorders (1980) J Endocrinol Invest, 3 (3), pp. 283-292Niccoli, P., Wion-Barbot, N., Caron, P., Henry, J.F., de Micco, C., Saint Andre, J.P., Interest of routine measurement of serum calcitonin: Study in a large series of thyroidectomized patients. The French Medullary Study Group (1997) J Clin Endocrinol Metab, 82 (2), pp. 338-341Gagel, R.F., Hoff, A.O., Cote, G.J., Medullary thyroid carcinoma (2005) Werner and Ingbar's the Thyroid: A Fundamental and Clinical Text, pp. 967-988. , In: Lewis E, Robert D, Sidney H, Sidney C, (Eds)., Philadelphia: Lippincott Williams and WilkinsPapini, E., Guglielmi, R., Bianchini, A., Crescenzi, A., Taccogna, S., Nardi, F., Risk of malignancy in nonpalpable thyroid nodules: Predictive value of ultrasound and color-Doppler features (2002) J Clin Endocrinol Metab, 87 (5), pp. 1941-1946Camargo, R.Y., Tomimori, E.K., Knobel, M., Medeiros-Neto, G., Preoperative assessment of thyroid nodules: Role of ultrasonography and fine needle aspiration biopsy followed by cytology (2007) Clinics, 62 (4), pp. 411-418Kang, H.W., No, J.H., Chung, J.H., Min, Y.K., Lee, M.S., Lee, M.K., Prevalence, clinical and ultrasonographic characteristics of thyroid incidentalomas (2004) Thyroid, 14 (1), pp. 29-33Shimura, H., Haraguchi, K., Hiejima, Y., Fukunari, N., Fujimoto, Y., Katagiri, M., Distinct diagnostic criteria for ultrasonographic examination of papillary thyroid carcinoma: A multicenter study (2005) Thyroid, 15 (3), pp. 251-258Cappelli, C., Castellano, M., Pirola, I., Cumetti, D., Agosti, B., Gandossi, E., The predictive value of ultrasound findings in the management of thyroid nodules (2007) Qjm, 100 (1), pp. 29-35Holden, A., The role of colour and duplex Doppler ultrasound in the assessment of thyroid nodules (1995) Australas Radiol, 39 (4), pp. 343-349Papini, E., Guglielmi, R., Bianchini, A., Crescenzi, A., Taccogna, S., Nardi, F., Risk of malignancy in nonpalpable thyroid nodules: Predictive value of ultrasound and color-Doppler features (2002) J Clin Endocrinol Metab, 87 (5), pp. 1941-1946Chammas, M.C., Gerhard, R., de Oliveira, I.R., Widman, A., de Barros, N., Durazzo, M., Thyroid nodules: Evaluation with power Doppler and duplex Doppler ultrasound (2005) Otolaryngol Head Neck Surg, 132 (6), pp. 874-882Frates, M.C., Benson, C.B., Doubilet, P.M., Cibas, E.S., Marqusee, E., Can color Doppler sonography aid in the prediction of malignancy of thyroid nodules? (2003) J Ultrasound Med, 22 (2), pp. 127-131Rago, T., Vitti, P., Chiovato, L., Mazzeo, S., de Liperi, A., Miccoli, P., Role of conventional ultrasonography and color flow-doppler sonography in predicting malignancy in 'cold' thyroid nodules (1998) Eur J Endocrinol, 138 (1), pp. 41-46Lyshchik, A., Moses, R., Barnes, S.L., Higashi, T., Asato, R., Miga, M.I., Quantitative analysis of tumor vascularity in benign and malignant solid thyroid nodules (2007) J Ultrasound Med, 26 (6), pp. 837-846Tamsel, S., Demirpolat, G., Erdogan, M., Nart, D., Karadeniz, M., Uluer, H., Power Doppler US patterns of vascularity and spectral Doppler US parameters in predicting malignancy in thyroid nodules (2007) Clin Radiol, 62 (3), pp. 245-251Pacini, F., Burroni, L., Ciuoli, C., di Cairano, G., Guarino, E., Management of thyroid nodules: A clinicopathological, evidence-based approach (2004) Eur J Nucl Med Mol Imaging, 31 (10), pp. 1443-1449Kim, T.Y., Kim, W.B., Ryu, J.S., Gong, G., Hong, S.J., Shong YK. 18F-fluorodeoxyglucose uptake in thyroid from positron emission tomogram (PET) for evaluation in cancer patients: High prevalence of malignancy in thyroid PET incidentaloma (2005) Laryngoscope, 115 (6), pp. 1074-1078Danese, D., Sciacchitano, S., Farsetti, A., Andreoli, M., Pontecorvi, A., Diagnostic accuracy of conventional versus sonography-guided fine-needle aspiration biopsy of thyroid nodules (1998) Thyroid, 8 (1), pp. 15-21de la Serna Saravia, C., Cuellar, F., Accuracy of aspiration cytology in thyroid cancer: A study in 1 institution (2006) Acta Cytol, 50 (4), pp. 384-387Giorgadze, T., Rossi, E.D., Fadda, G., Gupta, P.K., Livolsi, V.A., Baloch, Z., Does the fine-needle aspiration diagnosis of "Hurthle-cell neoplasm/follicular neoplasm with oncocytic features" denote increased risk of malignancy? (2004) Diagn Cytopathol, 31 (5), pp. 307-312Niepomniszcze, H., Garcia, A., Faure, E., Castellanos, A., del Carmen Zalazar, M., Bur, G., Long-term follow-up of contralateral lobe in patients hemithyroidectomized for solitary follicular adenoma (2001) Clin Endocrinol (oxf), 55 (4), pp. 509-513Alcantara-Jones, D.M., Araujo, L.M., Almeida, A.M., Jones, D.A., Cardoso, L.J., Passos, M.C., Percutaneous ethanol injection for the treatment of thyroid nodules (2006) Arq Bras Endocrinol Metabol, 50 (1), pp. 97-104Lippi, F., Ferrari, C., Manetti, L., Rago, T., Santini, F., Monzani, F., Treatment of solitary autonomous thyroid nodules by percutaneous ethanol injection: Results of an Italian multicenter study. The Multicenter Study Group (1996) J Clin Endocrinol Metab, 81 (9), pp. 3261-3264Hegedüs, L., Hansen, B.M., Knudsen, N., Hansen, J.M., Reduction of size of thyroid with radioactive iodine in multinodular non-toxic goitre (1988) Bmj, 297 (6649), pp. 661-662Huysmans, D., Hermus, A., Edelbroek, M., Barentsz, J., Corstens, F., Kloppenborg, P., Radioiodine for nontoxic multinodular goiter (1997) Thyroid, 7 (2), pp. 235-239Nygaard, B., Hegedus, L., Ulriksen, P., Nielsen, K.G., Hansen, J.M., Radioiodine therapy for multinodular toxic goiter (1999) Arch Intern Med, 159 (12), pp. 1364-1368Huysmans, D.A., Hermus, A.R., Corstens, F.H., Barentsz, J.O., Kloppenborg, P.W., Large, compressive goiters treated with radioiodine (1994) Ann Intern Med, 121 (10), pp. 757-762Nygaard, B., Soes-Petersen, U., Hoilund-Carlsen, P.F., Veje, A., Holst, P.E., Vestergaard, A., Improvement of upper airway obstruction after 131I-treatment of multinodular nontoxic goiter evaluated by flow volume loop curves (1996) J Endocrinol Invest, 19 (2), pp. 71-75Nygaard, B., Faber, J., Hegedus, L., Acute changes in thyroid volume and function following 131I therapy of multinodular goitre (1994) Clin Endocrinol (oxf), 41 (6), pp. 715-718Huysmans, D.A., Nieuwlaat, W.A., Erdtsieck, R.J., Schellekens, A.P., Bus, J.W., Bravenboer, B., Administration of a single low dose of recombinant human thyrotropin significantly enhances thyroid radioiodide uptake in nontoxic nodular goiter (2000) J Clin Endocrinol Metab, 85 (10), pp. 3592-3596Nieuwlaat, W.A., Hermus, A.R., Sivro-Prndelj, F., Corstens, F.H., Huysmans, D.A., Pretreatment with recombinant human TSH changes the regional distribution of radioiodine on thyroid scintigrams of nodular goiters (2001) J Clin Endocrinol Metab, 86 (11), pp. 5330-5336Nieuwlaat, W.A., Huysmans, D.A., van den Bosch, H.C., Sweep, C.G., Ross, H.A., Corstens, F.H., Pretreatment with a single, low dose of recombinant human thyrotropin allows dose reduction of radioiodine therapy in patients with nodular goiter (2003) J Clin Endocrinol Metab, 88 (7), pp. 3121-3129Duick, D.S., Baskin, H.J., Utility of recombinant human thyrotropin for augmentation of radioiodine uptake and treatment of nontoxic and toxic multinodular goiters (2003) Endocr Pract, 9 (3), pp. 204-209Silva, M.N., Rubio, I.G., Romao, R., Gebrin, E.M., Buchpiguel, C., Tomimori, E., Administration of a single dose of recombinant human thyrotrophin enhances the efficacy of radioiodine treatment of large compressive multinodular goitres (2004) Clin Endocrinol (oxf), 60 (3), pp. 300-308Albino, C.C., Mesa Jr., C.O., Olandoski, M., Ueda, C.E., Woellner, L.C., Goedert, C.A., Recombinant human thyrotropin as adjuvant in the treatment of multinodular goiters with radioiodine (2005) J Clin Endocrinol Metab, 90 (5), pp. 2775-2780Friguglietti, C.U., Lin, C.S., Kulcsar, M.A., Total thyroidectomy for benign thyroid disease (2003) Laryngoscope, 113 (10), pp. 1820-1826Rezzonico, J., Rezzonico, M., Pusiol, E., Pitoia, F., Neipomniszcze, H., Introducing the thyroid gland as another victim of the insulin resistance syndrome (2008) Thyroid, 18 (4), pp. 461-464Vella, V., Sciacca, L., Pandini, G., Mineo, R., Squatrito, S., Vigneri, R., The IGF system in thyroid cancer: New concepts (2001) Mol Pathol, 54 (3), pp. 121-124Rezzonico, J., Rezzonico, M., Pusiol, E., Pitoia, F., Neipomniszcze, H., 2008 Metformin treatment of benign thyroid nodules in euthytoid patients with insulin resistance (2008) Diabetes Vasc Dis Reas, 5, p. 223Papini, E., Guglielmi, R., Bizzarri, G., Graziano, F., Bianchini, A., Brufani, C., Pacella, S., Pacella, C.M., Treatment of benign cold thyroid nodules: A randomized clinical trial of percutaneous lases ablation versus levothyroxine therapy or follow-up (2007) Thyroid, pp. 229-235Spiezia, S., Garberoglio, R., Milone, F., Ramundo, V., Caiazzo, C., Assanti, A.P., Thyroid nodules and related symptoms are stably controlled two years after radiofrequency thermal ablation (2009) Thyroid, 19 (3), pp. 219-225Alexander, E.K., Hurwitz, S., Heering, J.P., Benson, C.B., Frates, M.C., Doubilet, P.M., Natural history of benign solid and cystic thyroid nodules (2003) Ann Intern Med, 138 (4), pp. 315-318Carmeci, C., Jeffrey, R.B., McDougall, I.R., Nowels, K.W., Weigel, R.J., Ultrasound-guided fine-needle aspiration biopsy of thyroid masses (1998) Thyroid, 8 (4), pp. 283-289Ylagan, L.R., Farkas, T., Dehner, L.P., Fine needle aspiration of the thyroid: A cytohistologic correlation and study of discrepant cases (2004) Thyroid, 14 (1), pp. 35-41Hung, W., Anderson, K.D., Chandra, R.S., Kapur, S.P., Patterson, K., Randolph, J.G., Solitary thyroid nodules in 71 children and adolescents (1992) J Pediatr Surg, 27 (11), pp. 1407-1409Yip, F.W., Reeve, T.S., Poole, A.G., Delbridge, L., Thyroid nodules in childhood and adolescence (1994) Aust N Z J Surg, 64 (10), pp. 676-678Hegedus, L., Clinical practice. The thyroid nodule (2004) N Engl J Med, 351 (17), pp. 1764-1771Niedziela, M., Pathogenesis, diagnosis and management of thyroid nodules in children (2006) Endocr Relat Cancer, 13 (2), pp. 427-453Degnan, B.M., McClellan, D.R., Francis, G.L., An analysis of fine-needle aspiration biopsy of the thyroid in children and adolescents (1996) J Pediatr Surg, 31 (7), pp. 903-907Lugo-Vicente, H., Ortiz, V.N., Irizarry, H., Camps, J.I., Pagan, V., Pediatric thyroid nodules: Management in the era of fine needle aspiration (1998) J Pediatr Surg, 33 (8), pp. 1302-1305Corrias, A., Einaudi, S., Chiorboli, E., Weber, G., Crino, A., Andreo, M., Accuracy of fine needle aspiration biopsy of thyroid nodules in detecting malignancy in childhood: Comparison with conventional clinical, laboratory, and imaging approaches (2001) J Clin Endocrinol Metab, 86 (10), pp. 4644-4648Amrikachi, M., Ponder, T.B., Wheeler, T.M., Smith, D., Ramzy, I., Thyroid fine-needle aspiration biopsy in children and adolescents: Experience with 218 aspirates (2005) Diagn Cytopathol, 32 (4), pp. 189-192Gharib, H., Papini, E., Valcavi, R., Baskin, H.J., Crescenzi, A., Dottorini, M.E., Duick, D.S., Zini, M., AACE/AME Task Force on Thyroid Nodules. American Association of Clinical Endocrinologists and Associazione Medici Endocrinologi medical guidelines for clinical practice for the diagnosis and management of thyroid nodules (2006) Endocr Pract, 12 (1), pp. 63-102Wiersinga, W.M., Management of thyroid nodules in children and adolescents (2007) Hormones (athens), 6 (3), pp. 194-199Moosa, M., Mazzaferri, E.L., Outcome of differentiated thyroid cancer diagnosed in pregnant women (1997) J Clin Endocrinol Metab, 82 (9), pp. 2862-286
Lower numbers of natural killer T cells in HIV-1 and Mycobacterium leprae co-infected patients
Natural killer T (NKT) cells are a heterogeneous population of lymphocytes that recognize antigens presented by CD1d and have attracted attention because of their potential role linking innate and adaptive immune responses. Peripheral NKT cells display a memory-activated phenotype and can rapidly secrete large amounts of pro-inflammatory cytokines upon antigenic activation. In this study, we evaluated NKT cells in the context of patients co-infected with HIV-1 and Mycobacterium leprae. The volunteers were enrolled into four groups: 22 healthy controls, 23 HIV-1-infected patients, 20 patients with leprosy and 17 patients with leprosy and HIV-1-infection. Flow cytometry and ELISPOT assays were performed on peripheral blood mononuclear cells. We demonstrated that patients co-infected with HIV-1 and M.leprae have significantly lower NKT cell frequencies [median 0.022%, interquartile range (IQR): 0.0070.051] in the peripheral blood when compared with healthy subjects (median 0.077%, IQR: 0.0320.405, P < 0.01) or HIV-1 mono-infected patients (median 0.072%, IQR: 0.0300.160, P < 0.05). Also, more NKT cells from co-infected patients secreted interferon-? after stimulation with DimerX, when compared with leprosy mono-infected patients (P = 0.05). These results suggest that NKT cells are decreased in frequency in HIV-1 and M.leprae co-infected patients compared with HIV-1 mono-infected patients alone, but are at a more activated state. Innate immunity in human subjects is strongly influenced by their spectrum of chronic infections, and in HIV-1-infected subjects, a concurrent mycobacterial infection probably hyper-activates and lowers circulating NKT cell numbers.National Institutes of Health [R01-AI52731, AI060379]Fogarty International Center [D43 TW00003]Fundacao de Amparo a Pesquisa do Estado de Sao Paulo [04/15856-9/Kallas, 2010/05845-0/Kallas]Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)Brazilian Ministry of Science and Technology [484230/2011-5]New York Community Trus
Role of chymase in cigarette smoke-induced pulmonary artery remodeling and pulmonary hypertension in hamsters
<p>Abstract</p> <p>Background</p> <p>Cigarette smoking is an important risk factor for pulmonary arterial hypertension (PAH) in chronic obstructive pulmonary disease (COPD). Chymase has been shown to function in the enzymatic production of angiotensin II (AngII) and the activation of transforming growth factor (TGF)-β1 in the cardiovascular system. The aim of this study was to determine the potential role of chymase in cigarette smoke-induced pulmonary artery remodeling and PAH.</p> <p>Methods</p> <p>Hamsters were exposed to cigarette smoke; after 4 months, lung morphology and tissue biochemical changes were examined using immunohistochemistry, Western blotting, radioimmunoassay and reverse-transcription polymerase chain reaction.</p> <p>Results</p> <p>Our results show that chronic cigarette smoke exposure significantly induced elevation of right ventricular systolic pressures (RVSP) and medial hypertrophy of pulmonary arterioles in hamsters, concurrent with an increase of chymase activity and synthesis in the lung. Elevated Ang II levels and enhanced TGF-β1/Smad signaling activation were also observed in smoke-exposed lungs. Chymase inhibition with chymostatin reduced the cigarette smoke-induced increase in chymase activity and Ang II concentration in the lung, and attenuated the RVSP elevation and the remodeling of pulmonary arterioles. Chymostatin did not affect angiotensin converting enzyme (ACE) activity in hamster lungs.</p> <p>Conclusions</p> <p>These results suggest that chronic cigarette smoke exposure can increase chymase activity and expression in hamster lungs. The capability of activated chymase to induce Ang II formation and TGF-β1 signaling may be part of the mechanism for smoking-induced pulmonary vascular remodeling. Thus, our study implies that blockade of chymase might provide benefits to PAH smokers.</p
Leukocyte Attraction by CCL20 and Its Receptor CCR6 in Humans and Mice with Pneumococcal Meningitis
We previously identified CCL20 as an early chemokine in the cerebrospinal fluid (CSF) of patients with pneumococcal meningitis but its functional relevance was unknown. Here we studied the role of CCL20 and its receptor CCR6 in pneumococcal meningitis. In a prospective nationwide study, CCL20 levels were significantly elevated in the CSF of patients with pneumococcal meningitis and correlated with CSF leukocyte counts. CCR6 deficient mice with pneumococcal meningitis and WT mice with pneumococcal meningitis treated with anti-CCL20 antibodies both had reduced CSF white blood cell counts. The reduction in CSF pleocytosis was also accompanied by an increase in brain bacterial titers. Additional in vitro experiments showed direct chemoattractant activity of CCL20 for granulocytes. In summary, our results identify the CCL20-CCR6 axis as an essential component of the innate immune defense against pneumococcal meningitis, controlling granulocyte recruitment
Innate Immune Responses of Pulmonary Epithelial Cells to Burkholderia pseudomallei Infection
10.1371/journal.pone.0007308PLoS ONE410
Osteoclast Activated FoxP3+ CD8+ T-Cells Suppress Bone Resorption in vitro
BACKGROUND: Osteoclasts are the body's sole bone resorbing cells. Cytokines produced by pro-inflammatory effector T-cells (T(EFF)) increase bone resorption by osteoclasts. Prolonged exposure to the T(EFF) produced cytokines leads to bone erosion diseases such as osteoporosis and rheumatoid arthritis. The crosstalk between T-cells and osteoclasts has been termed osteoimmunology. We have previously shown that under non-inflammatory conditions, murine osteoclasts can recruit naïve CD8 T-cells and activate these T-cells to induce CD25 and FoxP3 (Tc(REG)). The activation of CD8 T-cells by osteoclasts also induced the cytokines IL-2, IL-6, IL-10 and IFN-γ. Individually, these cytokines can activate or suppress osteoclast resorption. PRINCIPAL FINDINGS: To determine the net effect of Tc(REG) on osteoclast activity we used a number of in vitro assays. We found that Tc(REG) can potently and directly suppress bone resorption by osteoclasts. Tc(REG) could suppress osteoclast differentiation and resorption by mature osteoclasts, but did not affect their survival. Additionally, we showed that Tc(REG) suppress cytoskeletal reorganization in mature osteoclasts. Whereas induction of Tc(REG) by osteoclasts is antigen-dependent, suppression of osteoclasts by Tc(REG) does not require antigen or re-stimulation. We demonstrated that antibody blockade of IL-6, IL-10 or IFN-γ relieved suppression. The suppression did not require direct contact between the Tc(REG) and osteoclasts. SIGNIFICANCE: We have determined that osteoclast-induced Tc(REG) can suppress osteoclast activity, forming a negative feedback system. As the CD8 T-cells are activated in the absence of inflammatory signals, these observations suggest that this regulatory loop may play a role in regulating skeletal homeostasis. Our results provide the first documentation of suppression of osteoclast activity by CD8 regulatory T-cells and thus, extend the purview of osteoimmunology
Paracoccidioidomycosis of external genitalia: report of six new cases and review of the literature
Bioequivalência de Preparações Comerciais de L-Tiroxina (100 e 200µg): Avaliação em Pacientes Hipotireóideos Previamente Tireoidectomizados
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