Estrategia quirúrgica reconstructiva en un caso de duplication palatina compleja / Surgical reconstructive approach in a case of complex palatine duplication

La duplicación palatina es una malformación congénita rara de las estructuras craneofaciales. En la mayoría de casos se asocia a otras malformaciones faciales de diferente grado de severidad. Presentamos el caso de un paciente con duplicación de paladar y fisuras faciales raras, con el planteamiento y la estrategia quirúrgica para su reconstrucción. Con el apoyo de las imágenes escenográficas con reconstrucción tridimensional se realizó el planeamiento quirúrgico. Programamos resección en cuna de los segmentos mediales de cada paladar, a cada lado de la fisura facial, y transferencia medial en bloque del maxilar comprometido. La gran variación anatómica encontrada durante el procedimiento, 2 orificios infraorbitarios divididos por la fisura facial, y la alteración del seno maxilar del lado comprometido, nos impusieron un reto quirúrgico para la reconstrucción. Logramos la resección en bloque planeada recreando un único paladar. La evolución postoperatoria fue favorable, no se presentaron complicaciones y la oclusión funcional resultante fue la esperada (AU)

The palatine duplication is an uncommon congenital malformation of the craniofacial skeleton that is frequently associated to craniofacial malformations of different grades of severity. A case of palatine duplication associated to a rare craniofacial cleft, the planning and the surgical approach is presented. 3D reconstruction tomography images were used to guide the surgical planning. A wedge resection of both medial palatal arches with medial displacement were done. The highly disrupted maxillary anatomy made the reconstruction planning a surgical challenge. The wedge resection successfully achieves a single and anatomical palate. The postoperative follow shown no complications and the desired occlusion was obtained (AU)

Interleukin-15 receptor α on hepatic stellate cells regulates hepatic fibrogenesis in mice.

BACKGROUND & AIMS: Interleukin-15 (IL-15) and its high affinity receptor interleukin-15 receptor alpha (IL-15Rα) are widely expressed in immune cells and hepatic resident cells. IL-15 signaling has important functions in homeostasis of natural killer (NK), natural killer T (NKT) and cytotoxic T (CD8(+) T) cells, and in liver regeneration. We hypothesized that IL-15 has a protective role in liver fibrosis progression by maintaining NK cell homeostasis. METHODS: Fibrosis was induced using two mechanistically distinct models. Congenic bone marrow transplantation was used to evaluate the contribution of IL-15 signaling from various compartments to NK, CD8(+) T and NKT cell homeostasis and fibrogenesis. The gene expression profile of hepatic stellate cell (HSC) from IL-15Rα knockout (IL-15RαKO) mice and wild-type mice were captured using microarray analysis and validated in isolated HSC. Quantitative real-time PCR was used to assess repressors of collagen transcription. RESULTS: IL-15RαKO mice exhibited more fibrosis in both models. IL-15 signaling from specific types of hepatic cells had divergent roles in maintaining liver NK, CD8(+) T and NKT cells, with a direct and protective role on radio-resistant non-parenchymal cells beyond the control of NK homeostasis. HSCs isolated from IL-15RαKO mice demonstrated upregulation of collagen production. Finally, IL-15RαKO HSC with or without transforming growth factor beta (TGF-ß) stimulation exhibited increased expression of fibrosis markers and decreased collagen transcription repressors expression. CONCLUSIONS: IL-15Rα signaling has a direct anti-fibrotic effect independent of preserving NK homeostasis. These findings establish a rationale to further explore the anti-fibrotic potential of enhancing IL-15 signaling in HSCs. LAY SUMMARY: We investigated how a cellular protein, Interleukin-15 (IL-15), decreases the amount of scar tissue that is formed upon liver injury. We found that IL-15 and its receptor decrease the amount of scar tissue that is created by specialized liver cells (called stellate cells) and increase the number of a specific subgroup of immune cells (natural killer cells) that are known to eliminate stellate cells. TRANSCRIPT PROFILING ACCESSION NUMBER: GSE45612, GSE 68001 and GSE 25097.

Dendritic cell regulation of carbon tetrachloride-induced murine liver fibrosis regression.

UNLABELLED: Although hepatic fibrosis typically follows chronic inflammation, fibrosis will often regress after cessation of liver injury. In this study, we examined whether liver dendritic cells (DCs) play a role in liver fibrosis regression using carbon tetrachloride to induce liver injury. We examined DC dynamics during fibrosis regression and their capacity to modulate liver fibrosis regression upon cessation of injury. We show that conditional DC depletion soon after discontinuation of the liver insult leads to delayed fibrosis regression and reduced clearance of activated hepatic stellate cells, the key fibrogenic cell in the liver. Conversely, DC expansion induced either by Flt3L (fms-like tyrosine kinase-3 ligand) or adoptive transfer of purified DCs accelerates liver fibrosis regression. DC modulation of fibrosis was partially dependent on matrix metalloproteinase (MMP)-9, because MMP-9 inhibition abolished the Flt3L-mediated effect and the ability of transferred DCs to accelerate fibrosis regression. In contrast, transfer of DCs from MMP-9-deficient mice failed to improve fibrosis regression. CONCLUSION: Taken together, these results suggest that DCs increase fibrosis regression and that the effect is correlated with their production of MMP-9. The results also suggest that Flt3L treatment during fibrosis resolution merits evaluation to accelerate regression of advanced liver fibrosis.