Regulation of cell death receptor S-nitrosylation and apoptotic signaling by Sorafenib in hepatoblastoma cells.

Nitric oxide (NO) plays a relevant role during cell death regulation in tumor cells. The overexpression of nitric oxide synthase type III (NOS-3) induces oxidative and nitrosative stress, p53 and cell death receptor expression and apoptosis in hepatoblastoma cells. S-nitrosylation of cell death receptor modulates apoptosis. Sorafenib is the unique recommended molecular-targeted drug for the treatment of patients with advanced hepatocellular carcinoma. The present study was addressed to elucidate the potential role of NO during Sorafenib-induced cell death in HepG2 cells. We determined the intra- and extracellular NO concentration, cell death receptor expression and their S-nitrosylation modifications, and apoptotic signaling in Sorafenib-treated HepG2 cells. The effect of NO donors on above parameters has also been determined. Sorafenib induced apoptosis in HepG2 cells. However, low concentration of the drug (10nM) increased cell death receptor expression, as well as caspase-8 and -9 activation, but without activation of downstream apoptotic markers. In contrast, Sorafenib (10 µM) reduced upstream apoptotic parameters but increased caspase-3 activation and DNA fragmentation in HepG2 cells. The shift of cell death signaling pathway was associated with a reduction of S-nitrosylation of cell death receptors in Sorafenib-treated cells. The administration of NO donors increased S-nitrosylation of cell death receptors and overall induction of cell death markers in control and Sorafenib-treated cells. In conclusion, Sorafenib induced alteration of cell death receptor S-nitrosylation status which may have a relevant repercussion on cell death signaling in hepatoblastoma cells.

Estudio experimental sobre la regeneración ósea mandibular de la rata con diferentes biomateriales / Experimental study in rats of mandibular bone regeneration with different biomaterials

Objetivo. Los defectos óseos mandibulares resultantes de infecciones,traumatismos o resecciones oncológicas, van a producir severos problemas funcionalesy/o estéticos, que van a precisar de un tratamiento complejo. Durante losúltimos años, las aportaciones al terreno de la reconstrucción ósea se han debatidoentre métodos tan dispares como la distracción ósea o la utilización de colgajos libresmicrovascularizados, pasando por un sin fin de biomateriales. El objetivo de este estudiofue comparar la formación de hueso nuevo tras la aplicación de una membranareabsorbible y dos tipos de sustitutivos óseos. Material y método. Se utilizaron 24ratas adultas macho tipo Wistar, en las que se crearon defectos circulares de 4 mmde diámetro en ambos lados de la mandíbula. Se formaron 4 grupos, un grupo controly 3 grupos experimentales. Los animales fueron sacrificados a las 3 y 6 semanasde la cirugía, realizándose un análisis radiológico e histológico. Resultados. Los defectoscontrol no mostraron formación ósea, apareciendo una reparación por tejidofibroso. La membrana de hueso utilizada de forma aislada, actuó como una barreraeficaz excluyendo los tejidos no osteogénicos, pero no se produjo reparación totaldel defecto en ningún caso. El grupo de Colloss® y membrana, mostró una regeneraciónósea completa del defecto a las 6 semanas. El grupo de NovaBone® y membrana,no mostró formación ósea, apareciendo las partículas del biomaterial ocupandoel defecto. Conclusiones. La regeneración ósea fue significativamente mayoren los defectos rellenos con Colloss® y cubiertos con la membrana de Lambone®,comparado con los otros grupos experimentales(AU)

Objective. Mandibular bone defects can occur as a resultof trauma, neoplasm, or infectious conditions. Such conditions oftenare associated with severe funtional and esthetic problems. Correctivetreatment often is complicated by limitations in tissue adaptation.The aim of this study was to compare new bone formation followingapplication of a bioabsorbable membrane and two types of bonesubstitutes. Material and method. In the present study, 24 fourmonth-old male Wistar rats were used. Standardized round throughand-through bone defects (4 mm in diameter) were made in bothmandibles and the rats were divided into four groups: one controlgroup and 3 experimental groups. Animals were killed 3 and 6 weeksafter surgery. Bone defect healing was assessed by radiologic andhistologic analysis. Results. The control defects showed no boneformation; holes were filled with fibrous connective tissue. Bonemembrane alone was an efficient barrier, excluding nonosteogenictissue. However, new bone formation underneath the membranewas incomplete. The Colloss® + membrane group showed completehealing after 6 weeks. The NovaBone® + membrane group showedno bone formation and particles appeared in the defect. Conclusions.The percentage bone regeneration was significantly better in thedefects filled with Colloss® and covered with Lambone® than theother experimental groups(AU)

Disnea, tos y masa pulmonar / Eighty-five year old male patient with a subcutaneous mass in the right costal area

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Intervellositis histiocítica crónica y aborto de repetición / Chronic histiocytic intervillositis and recurrent miscarriage

La intervellositis histiocítica crónica (TVHC) es una infrecuente lesión placentaria, de posible origen inmunológico. Se ha asociado con abortos de repetición y resultados adversos en el embarazo. Se caracteriza por la presencia de un abundante infiltrado inflamatorio en el espacio intervelloso, compuesto principalmente por monocitos y macrófagos. El diagnóstico diferencial incluye varias entidades, y por el momento no pueden descartarse causas infecciosas (AU)

Repair of experimental mandibular defects in rats with autogenous, demineralised, frozen and fresh bone.

This prospective experimental study aimed to assess the regenerative capability of demineralised bone autografts resected and replaced orthotopically, compared with traditional fresh and deep frozen mandibular autografts in rats. In 60 adult Wistar rats, a bone defect 4 x 4 mm was created at the left ascending mandibular ramus and the removed bone was used as a fresh (n = 20), deep frozen (n = 20), or demineralised (n = 20) graft which was implanted orthotopically 2 weeks later. Ten rats in each group were killed at 2 and 6 weeks later. Outcome was measured by cellular proliferation on histological examination. The number of mesenchymal cells was significantly greater (P < 0.05) at both 2 and 6 weeks in the demineralised grafts than in the other two groups. There were no differences between the 2- and 6-week examinations of deep frozen bone, nor between the medullary and peripheral aspects. It was concluded that demineralised bony autografts cause greater osteoinduction both in the short (2 weeks) and the medium (6 weeks) term.

[Trousseau's syndrome in lung adenocarcinoma. The rare appearance of venous gangrene]. / Síndrome de Trousseau en adenocarcinoma de pulmón. La infrecuente aparición de la gangrena venosa.

Trousseau's syndrome includes a wide range of coagulation disorders, migratory thrombotic phenomena being the main associated entities. Treatment is difficult and venous gangrene constitutes a rare but deadly final stage that is particularly painful for the patient. The outlook after treatment is poor.

[Idiopathic ulcer of the small intestine]. / Ulceración idiopática del intestino delgado.

Two cases of multiple idiopathic ulcers of the small intestine are reported, which were found in two aged patients with a significant history of vascular pathology. Despite this, the pathological examination of the surgical specimens could not demonstrate a vascular origin of such lesions.