Sex hormone modulation of cell growth and apoptosis of the human monocytic/macrophage cell line

Sex hormones seem to modulate the immune/inflammatory responses by different mechanisms in female and male rheumatoid arthritis patients. The effects of 17β-oestradiol and of testosterone were tested on the cultured human monocytic/macrophage cell line (THP-1) activated with IFN-γ in order to investigate their role in cell proliferation and apoptosis. Activated human THP-1 cells were cultured in the presence of 17β-oestradiol and testosterone (final concentration, 10 nM). The evaluation of markers of cell proliferation included the NF-κB DNA-binding assay, the NF-κB inhibition complex, the proliferating cell nuclear antigen expression and the methyl-tetrazolium salt test. Apoptosis was detected by the annexin V-propidium assay and by the cleaved poly-ADP ribose polymerase expression. Specific methods included flow analysis cytometry scatter analysis, immunocytochemistry and western blot analysis. Cell growth inhibition and increased apoptosis were observed in testosterone-treated THP-1 cells. Increased poly-ADP ribose polymerase-cleaved expression and decreased proliferating cell nuclear antigen expression, as well as an increase of IκB-α and a decrease of the IκB-α phosphorylated form (ser 32), were found in testosterone-treated THP-1 cells. However, the NF-κB DNA binding was found increased in 17β-oestradiol-treated THP-1 cells. The treatment with staurosporine (enhancer of apoptosis) induced decreased NF-κB DNA binding in all conditions, but particularly in testosterone-treated THP-1 cells. Treatment of THP-1 by sex hormones was found to influence cell proliferation and apoptosis. Androgens were found to increase the apoptosis, and oestrogens showed a protective trend on cell death – both acting as modulators of the NF-κB complex

Momentum distribution of charm hadrons in a fluid-dynamic approach

Exploiting a mapping between transport theory and fluid dynamics, we show how a fluid-dynamic description of the diffusion of charm quarks in the QCD plasma is feasible. We show results for spectra of charmed hadrons obtained with a fluid-dynamic description of the quark-gluon plasma (QGP) coupled with the conservation of a heavy-quark - antiquark current. We compare our calculations with the most recent experimental data in order to provide further constraints on the transport coefficients of the QGP.Comment: Hard Probes 202

Fluid dynamics of charm quarks in the quark--gluon plasma

A fluid-dynamic approach to charm-quark diffusion in the quark-gluon plasma (QGP) is developed for the first time. Results for integrated yields and momentum distributions of charmed hadrons obtained with a fluid-dynamic description for the dynamics of the QGP coupled to an additional heavy-quark-antiquark current are shown. In addition to the thermodynamic Equation of State (EoS), this description uses a heavy-quark diffusion constant which we take from Lattice QCD calculations. The results describe quantitatively experimental data measured at the LHC at the center-of-mass energy of $\sqrt{s_{\rm NN}}$ = 5.02 TeV up to $p_{\rm T}\sim$ 4-5 GeV/$c$, showing that charm quarks undergo a very fast hydrodynamization in the medium created by ultrarelativistic heavy-ion collisions.Comment: 11 pages, 6 figure

Cryptococcosis mimicking cutaneous cellulitis in a patient suffering from rheumatoid arthritis: a case report

<p>Abstract</p> <p>Background</p> <p><it>Cryptococcus neoformans </it>is an encapsulated yeast and the most frequent cryptococcal species found in humans. Cryptococcosis is considered an opportunistic infection as it affects mainly immunosuppressed individuals. In humans, <it>C. neoformans </it>causes three types of infections: pulmonary cryptococcosis, cryptococcal meningitis and wound or cutaneous cryptococcosis.</p> <p>Case Presentation</p> <p>An 81-year-old woman developed severe necrotizing cellulitis on her left arm without any preceding injury. The patient had been treated with systemic corticosteroids over twenty years for rheumatoid arthritis (RA). Skin biopsies of the wound area were initially interpreted as cutaneous vasculitis of unknown etiology. However, periodic acid Schiff staining and smear analysis later revealed structures consistent with <it>Cryptococcus neoformans</it>, and the infection was subsequently confirmed by culture. After the initiation of therapy with fluconazole 400 mg per day the general condition and the skin ulcers improved rapidly and the patient was discharged to a rehabilitation facility. Subsequently surgical debridement and skin grafting were performed.</p> <p>Conclusions</p> <p>Opportunistic infections such as cryptococcosis can clinically and histologically mimic cutaneous vasculitis and have to be investigated rigorously as a differential diagnosis in immunosuppressed patients.</p

Anti-inflammatory effects of cell-based therapy with tyrosine hydroxylase-positive catecholaminergic cells in experimental arthritis

Objectives: Studies in rheumatoid arthritis (RA), osteoarthritis (OA) and mice with arthritis demonstrated tyrosine hydroxylase-positive (TH+) cells in arthritic synovium and parallel loss of sympathetic nerve fibres. The exact function of TH+ cells and mode of TH induction are not known. Methods: Synovial cells of RA/OA were isolated and cultured under normoxic/hypoxic conditions with/without stimulating enzyme cofactors of TH and inhibitors of TH. We studied TH expression and release of cytokines/catecholamines. In vivo function was tested by cell therapy with TH+ neuronal precursor cells (TH+ neuronal cells) in DBA/1 mice with collagen type II-induced arthritis (CIA). Results: Compared with normoxic conditions, hypoxia increased TH protein expression and catecholamine synthesis and decreased release of tumour necrosis factor (TNF) in OA/RA synovial cells. This inhibitory effect on TNF was reversed by TH inhibition with α-methyl-para-tyrosine (αMPT), which was particularly evident under hypoxic conditions. Incubation with specific TH cofactors (tetrahydrobiopterin and Fe2+) increased hypoxia-induced inhibition of TNF, which was also reversed by αMPT. To address a possible clinical role of TH+ cells, murine TH+ neuronal cells were generated from mesenchymal stem cells. TH+ neuronal cells exhibited a typical catecholaminergic phenotype. Adoptive transfer of TH+ neuronal cells markedly reduced CIA in mice, and 6-hydroxydopamine, which depletes TH+ cells, reversed this effect. Conclusions: The anti-inflammatory effect of TH+ neuronal cells on experimental arthritis has been presented for the first time. In RA/OA, TH+ synovial cells have TH-dependent anti-inflammatory capacities, which are augmented under hypoxia. Using generated TH+ neuronal cells might open new avenues for cell-based therapy

Intra-articular glucocorticoid injections decrease the number of steroid hormone receptor positive cells in synovial tissue of patients with persistent knee arthritis

Objectives: To explore changes in the number of steroid hormone receptor positive cells in synovial tissue (ST) after intra-articular glucocorticoid injection, to correlate these changes with changes in clinical variables, and to evaluate whether the number of steroid hormone receptor positive cells predicted the clinical response to glucocorticoid injection. Methods: Fourteen patients with persistent knee arthritis despite at least two previous injections in an outpatient setting received an intra-articular injection with glucocorticoids, followed by 3 days of admission with bed rest. Clinical efficacy was assessed at 6 and 12 weeks. ST biopsies were performed 2 weeks before and 12 weeks after the injection. The presence of different cell types (T cells, macrophages, fibroblast-like synoviocytes) and numbers of glucocorticoid, androgen and oestrogen α and β receptor positive cells were evaluated by histochemistry. Results: Patients showed, despite previous failures, good clinical response to glucocorticoid injection, with significant improvement in erythrocyte sedimentation rate, visual analogue scale (VAS) for pain, and joint disability score. The number of steroid hormone receptor positive cells decreased markedly (p<0.05 for all four receptors). The decrease in oestrogen receptor α positive cells correlated significantly with the improvement in VAS for pain and joint disability score. The number of glucocorticoid, androgen and oestrogen α and β receptor positive cells before injection did not predict the effect of treatment. Conclusions: Intra-articular glucocorticoid injections followed by bed rest for persistent arthritis are clinically effective and significantly decrease the number of steroid hormone receptor positive cells in ST. The relevance of the latter needs further study

VIII Encuentro de Docentes e Investigadores en Historia del Diseño, la Arquitectura y la Ciudad

Acta de congresoLa conmemoración de los cien años de la Reforma Universitaria de 1918 se presentó como una ocasión propicia para debatir el rol de la historia, la teoría y la crítica en la formación y en la práctica profesional de diseñadores, arquitectos y urbanistas. En ese marco el VIII Encuentro de Docentes e Investigadores en Historia del Diseño, la Arquitectura y la Ciudad constituyó un espacio de intercambio y reflexión cuya realización ha sido posible gracias a la colaboración entre Facultades de Arquitectura, Urbanismo y Diseño de la Universidad Nacional y la Facultad de Arquitectura de la Universidad Católica de Córdoba, contando además con la activa participación de mayoría de las Facultades, Centros e Institutos de Historia de la Arquitectura del país y la región. Orientado en su convocatoria tanto a docentes como a estudiantes de Arquitectura y Diseño Industrial de todos los niveles de la FAUD-UNC promovió el debate de ideas a partir de experiencias concretas en instancias tales como mesas temáticas de carácter interdisciplinario, que adoptaron la modalidad de presentación de ponencias, entre otras actividades. En el ámbito de VIII Encuentro, desarrollado en la sede Ciudad Universitaria de Córdoba, se desplegaron numerosas posiciones sobre la enseñanza, la investigación y la formación en historia, teoría y crítica del diseño, la arquitectura y la ciudad; sumándose el aporte realizado a través de sus respectivas conferencias de Ana Clarisa Agüero, Bibiana Cicutti, Fernando Aliata y Alberto Petrina. El conjunto de ponencias que se publican en este Repositorio de la UNC son el resultado de dos intensas jornadas de exposiciones, cuyos contenidos han posibilitado actualizar viejos dilemas y promover nuevos debates. El evento recibió el apoyo de las autoridades de la FAUD-UNC, en especial de la Secretaría de Investigación y de la Biblioteca de nuestra casa, como así también de la Facultad de Arquitectura de la UCC; va para todos ellos un especial agradecimiento

Dopaminergic Agents in Rheumatoid Arthritis

Clinical evidences suggest a causal relationship between rheumatoid arthritis (RA) and the dopaminergic system, and several studies described an alteration of the disease in patients treated with dopaminergic agents. Despite these interesting results, potential direct effects of dopamine on RA have not been intensively considered until the last decade. Recent studies confirm a direct effect of dopamine on the systemic immune response as well as on bone remodeling and on joint inflammation, both in humans and in different animal models of arthritis. While more research is necessary to accurately determine the effect of dopamine in RA, these results are encouraging and support a possible use of dopaminergic drugs for the treatment of arthritis in the future. Moreover, they point out that dopaminergic agents use to treat comorbidities, might influence the immune response and the disease progression in RA patients. This review summarizes the current knowledge about the effects of dopaminergic drugs on RA and describes the potential of dopaminergic drugs as future therapeutic strategy in arthritis

Aromatase and regulation of the estrogen-to-androgen ratio in synovial tissue inflammation: common pathway in both sexes

Sex hormones play an active role in inflammatory responses, with androgens being anti-inflammatory, whereas estrogens have both pro- and anti-inflammatory effects. In rheumatoid arthritis (RA) patients, low levels of androgens and high levels of estrone are found in the synovial fluid. Aromatase is the key enzyme for the conversion of androgens into estrogens. Proinflammatory cytokines stimulate aromatase activity so that the inflammatory milieu can induce conversion of androgens to estrogens. Moreover, testosterone inhibits aromatase activity. As local androgen levels are low in RA, this can contribute to high aromatase activity in the synovium. Importantly, aromatase-converted estrogens are converted into proproliferative and proinflammatory 16-hydroxylated estrogens. A hormone involved in aromatase activity is vitamin D, which downregulates aromatase in human RA macrophages. Collectively, evidence suggests a key role of aromatase in sex hormone balance during chronic inflammation and points to the importance of vitamin D as a possible new tool for aromatase modulation