Síndrome adyuvante por implante de protesis mamarias de silicón (siliconosis): ¿una condición emergente? / Adjuvant syndrome due to silicone breast prosthesis implant (siliconosis): an emergent condition?

Los implantes mamarios de silicona se han asociado con una variedad de condiciones médicas que aparecen en coincidencia con su implantación; ello constituye la emergencia de una nueva y poco conocida patología de la modernidad. Más del 87% de los enfermos sintomáticos, presentan neuropatía desmielinizante y axonal, comprobada en la biopsia de nervio y músculo, mientras que aproximadamente el 22%-25% tienen evidencia de enfermedad tiroidea autoinmune. Un pequeño porcentaje del 10%-12%, presentan enfermedad desmielinizante primaria del sistema nervioso: esclerosis múltiple diagnósticada mediante resonancia magnética y estudios de líquido cefalorraquideo. Otros presentan condiciones inmunológicas diversas como síndrome de fibromialgia, tiroiditis de Hashimoto, polimiositis, dermatomiositis, lupus eritematoso sistémico, artritis reumatoide, esclerodermia y presencia de autoanticuerpos. Para estos pacientes sintomáticos se propone como diagnóstico unitario un síndrome adyuvante por implante de prótesis mamarias de silicon. Se presentan los casos de dos pacientes ilustrativos.

Silicone breast prosthesis has been associated with a variety of medical conditions or autoimmune diseases, which has coincidental relation with the implants insertion; it's loomed as a new and unknown pathology of the modern times. More than 87% of symptomatic patients developed demyelination axonal neuropathy demonstrated by nerve and muscle biopsy; 22% to 25% have evidence of autoimmune thyroid disease. An a small group of patients (10%-12%) have primary central nervous system demyelination disease as. multiple selerosis. The diagnosis of multiple selerosis was corroborated by magnetic resonance imaging and cerebrospinal fluid analysis. Also, an other wide spectrum of immunological diseases have been observed, such as fibromyalgia. Hashimoto's, polymyositis, dermatomyositis, lupus erythematosus, rheumatoid arthritis, scleroderma, and the presence of autoantibodies. Finally, for symptomatic patients, an adjuvant syndrome of silicone breast prosthesis or implant is proposed as a unitary diagnosis. The authors presented two patients whom illustrated this entity.

Tumor necrosis factor-like weak inducer of apoptosis is a mitogen for liver progenitor cells.

UNLABELLED: Liver progenitor cells (LPCs) represent the cell compartment facilitating hepatic regeneration during chronic injury while hepatocyte-mediated repair mechanisms are compromised. LPC proliferation is frequently observed in human chronic liver diseases such as hereditary hemochromatosis, fatty liver disease, and chronic hepatitis. In vivo studies have suggested that a tumor necrosis factor family member, tumor necrosis factor-like weak inducer of apoptosis (TWEAK), is promitotic for LPCs; whether it acts directly is not known. In our murine choline-deficient, ethionine-supplemented (CDE) model of chronic liver injury, TWEAK receptor [fibroblast growth factor-inducible 14 (Fn14)] expression in the whole liver is massively upregulated. We therefore set out to investigate whether TWEAK/Fn14 signaling promotes the regenerative response in CDE-induced chronic liver injury by mitotic stimulation of LPCs. Fn14 knockout (KO) mice showed significantly reduced LPC numbers and attenuated inflammation and cytokine production after 2 weeks of CDE feeding. The close association between LPC proliferation and activation of hepatic stellate cells in chronic liver injury prompted us to investigate whether fibrogenesis was also modulated in Fn14 KO animals. Collagen deposition and expression of key fibrogenesis mediators were reduced after 2 weeks of injury, and this correlated with LPC numbers. Furthermore, the injection of 2-week-CDE-treated wildtype animals with TWEAK led to increased proliferation of nonparenchymal pan cytokeratin-positive cells. Stimulation of an Fn14-positive LPC line with TWEAK led to nuclear factor kappa light chain enhancer of activated B cells (NFkappaB) activation and dose-dependent proliferation, which was diminished after targeting of the p50 NFkappaB subunit by RNA interference. CONCLUSION: TWEAK acts directly and stimulates LPC mitosis in an Fn14-dependent and NFkappaB-dependent fashion, and signaling via this pathway mediates the LPC response to CDE-induced injury and regeneration.

Blockade of the OX40 ligand prolongs corneal allograft survival.

Although corneal transplantation is one of the most common tissue transplantations and is known to have a high graft acceptance rate, occasional corneal graft rejection remains a cause of blindness. OX40, a member of the TNF receptor superfamily, is expressed on activated T cells, and transmits a costimulatory signal by binding to OX40 ligand (OX40L) expressed on several cells with antigen-presenting functions. Using a blocking monoclonal antibody (mAb) against murine OX40L, we investigated the role of OX40 in a murine model of corneal transplantation. C3H/He mouse corneas were transplanted to BALB/c mice orthotopically. Administration of anti-OX40L mAb significantly reduced allograft rejection, and increased graft survival rate to 40% at 8 weeks after transplantation, while all corneas were rejected within 5 weeks in control IgG-treated mice. Similar reduced rejection was observed when wild-type donor corneas were transplanted to OX40L-deficient recipients. In vitro study revealed that the anti-OX40L mAb treatment reduced proliferative response and IFN-gamma production of draining lymph node cells in response to stimulation with donor alloantigen. These results demonstrate that OX40L blockade is effective for prolongation of corneal allograft survival by inhibiting recipient T cell activation.

Physiology of fever.

Knowing how the body reacts to the presence of pathogens allows healthcare professionals to make informed decisions about what action to take in caring for the child with fever. A raised body temperature raises the metabolic rate and makes the immune response more efficient. It also stimulates naturally occurring anti-pyretics but can also have harmful effects. Careful monitoring based on risk of serious illness is recommended in new guidelines on the management of feverish illness in young children provide (National Institute of Health and Clinical Excellence (NICE 2007), which also provide an opportunity for standardising fever management.

Roles of OX40 in the development of murine experimental allergic conjunctivitis: exacerbation and attenuation by stimulation and blocking of OX40.

PURPOSE: To investigate the roles of interaction between OX40 and OX40 ligand (OX40L) in the development of experimental allergic conjunctivitis (EC) in mice. METHODS: BALB/c mice actively immunized with short ragweed pollen (RW) were intraperitoneally injected on days 0, 2, 4, 6, and 8 with agonistic anti-OX40 Ab, blocking anti-OX40L Ab, or normal rat (nr)IgG. On day 10, the mice were challenged with RW in eye drops, and 24 hours later their conjunctivas, spleens, and blood were harvested for analyses. For examination of the effects of the Abs during the late induction (or effector) phase, actively immunized mice were treated with the Abs just before or at the same time as the challenge. In addition, splenocytes from RW-primed mice were transferred into syngeneic naïve mice, and the recipients were treated with Abs twice (on days 2 and 4). On day 4, the mice were challenged with RW and evaluated. RESULTS: When the treatments were performed during the induction phase, anti-OX40 Ab treatment significantly increased clinical EC and eosinophil infiltration into the conjunctiva, whereas anti-OX40L Ab treatment significantly reduced eosinophil infiltration. Compared with splenocytes from nrIgG-treated mice, splenocytes from anti-OX40 Ab-treated mice proliferated vigorously against RW and produced significantly higher amounts of IL-2, -4, and -5 by RW stimulation but a significantly lesser amount of IFN-gamma after Con A stimulation. In contrast, splenocytes from anti-OX40L Ab-treated mice produced significantly less IL-5 with RW stimulation and IL-2 and IL-5 with Con A stimulation, whereas significantly more IFN-gamma was induced by Con A stimulation. Treatment with anti-OX40 and anti-OX40L Abs during the late induction or effector phase of EC did not affect eosinophil infiltration. CONCLUSIONS: Blocking of the interaction between OX40 and OX40L in vivo inhibits the development of EC. In contrast, forced stimulation of OX40 in vivo significantly exacerbates EC by activating T cells, especially Th2 cells. These effects were noted only in the induction phase of EC, suggesting that the interaction between OX40 and OX40L is important in the generation of Th2 immune responses in the development of EC.