Lipids: Role in Embryonic Development (Review)

Aims: We propose to briefly review the specific role of lipids in embryonic structures development. Results: Lipids are organic substances insoluble in water, divided into several classes, such as fatty acids, glycolipids, phospholipids, ceramides, sphingolipids, and stereo-lipids. They participate in processes of cellular metabolism and embryonic development which are associated with signalling, proliferation and cell migration. They act in developmental processes such as calcification and bone mineralization, pulmonary maturity, cellular differentiation, and neural survival, epithelial cells polarization and muscle formation, in which phospholipids as a major group, work more regularly. Lipids during embryonic development work directly as transport molecules or cell markers. In addition to an imbalance in its enzymatic and protein precursors (such as choline kinase), lipids can increase or decrease lipid concentration in cells, prevent its biotransformation, or affect its synergy with other molecules, leading to failures in the formation of organs such as the heart, brain, and bones. This aims to further the understanding of these processes and highlight its feasibility for future clinical applications. Conclusion: Lipids maintain cell membrane integrity in blastocysts, transport calcium to nerve and bone cells, facilitate neural apoptosis, and promote pulmonary maturation. These results aid in the understanding and prediction of alterations in lipidic metabolic syndromes in several pathological disorders during organ development.

Inhibidores de histidina decarboxilasa atenúan la actividad proangiogénica de células de Leydig tumorales: ¿Potencial terapia neoadyuvante para el tratamiento de leydigiomas? / Histidine decarboxylase inhibitors attenuate the pro angiogenic activity of Leydig tumor cells: Potential neoadjuvant therapy for the treatment of leydigiomas?

Resumen Los tumores de células de Leydig (TCL) son tumores endócrinos del intersticio testicular, cuya incidencia se encuentra en aumento. Los síntomas incluyen feminización o virilización en pacientes prepuberales, y pérdida de libido, disfunción eréctil, infertilidad y/o ginecomastia en adultos. Si bien son usualmente benignos, cuando malignizan en adultos no responden a radio y quimioterapia. Múltiples trabajos han reportado que la histidina decarboxilasa (HDC), enzima que cataliza la conversión de L-histidina en histamina (HA), tiene un rol importante en el desarrollo de tumores. A su vez, en nuestro laboratorio demostramos que la HA induce la proliferación de células de Leydig tumorales (CLT) murinas, mientras que la inhibición de HDC disminuye su proliferación y capacidad esteroidogénica. Además, observamos elevada expresión de HDC en TCL pediátricos vs. controles de distintos estadios de madurez sexual; y se ha descrito que ratones knock out para HDC poseen una angiogénesis incompleta. Para evaluar el rol de HDC en la modulación de la angiogénesis se empleó la línea de CLT de rata R2C, principal modelo utilizado en estudios de Leydigioma. También se realizaron estudios en TCL pediátricos. Los medios condicionados por las CLT R2C estimularon la angiogénesis tanto in vitro como in vivo (empleando HUVEC y analizando el grado de vascularización de membranas corioalantoideas de codorniz, respectivamente). El efecto in vitro se revirtió al tratar previamente las CLT R2C con α-metil-DL-histidinadihidrocloruro, inhibidor específico de HDC. A su vez, tanto la HA como los medios condicionados provenientes de TCL pediátricos, produjeron un aumento en la proliferación de las HUVEC. Nuestros resultados sugieren que las CLT producen HA y otros factores proangiogénicos, y que la inhibición selectiva de HDC atenúa la capacidad proangiogénica de las CLT. En base a estos resultados y evidencias previas del laboratorio, inhibidores específicos de HDC podrían ser utilizados como potencial terapia neoadyuvante en TCL.

ABSTRACT Leydig Cell tumors (LCT) are a rare group of endocrine tumors in the testicular interstitium. Between 1 and 3% of testicular malignances in adults and 4% in prepubertal children belong to LCT. An increasing incidence of this type of neoplasia has been reported recently all around the world. Particularly, a strong relationship between LCT and the use of anabolic steroids (which are commonly used nowadays) has been reported recently. In prepubertal boys, symptoms include feminization or virilization, depending on the major circulating steroid (estradiol or testosterone respectively). Adult patients show loss of libido, penile dysfunction, infertility and/or gynecomastia. Although the etiology still is unknown, several studies indicate that tumoral Leydig cells have an excessive production of insulin-like growth factor (IGF-1), as well as aromatase (CYP19) overexpression, which causes an enormous amount of estrogens (particularly estradiol, E2), and both factors play an important role in tumorigenesis. While usually benign, when LCT became malignant in adults they respond poorly to radio and chemotherapy. Likewise, it has been reported that both therapies increase the incidence of several tumors. All these data imply the need of new therapeutic targets to avoid the chirurgical dissection of the testes and the consequences of the hormonal therapies associated, which implicate not only the loss in reproductive function, but also psychological disorders. Several publications have reported that histidine decarboxylase (HDC), the only enzyme capable of catalyzing the conversion from L-histidine to histamine (HA) in mammals, has an important role in the development of several types of tumors, such as colorectal, breast and melanoma. At the same time, in our laboratory we have reported that HA induces cell proliferation of murine Leydig cells, and complementary, this cell proliferation decreases when inhibiting selectively HDC, as well as steroid synthesis (progesterone and E2). Also, we observed a higher expression of HDC in pediatric LCT (n = 3) than normal controls corresponding to different stages of sexual maturation (n = 9). It has been described that HDC knock out mice have an incomplete angiogenesis, and also that MA-10 Leydig cells HDC expression correlates with vascular endothelial growth factor (VEGF). The aim of this study is to improve our knowledge about the role of HDC in LCT biology, particularly, the angiogenesis modulation. We used the R2C Leydig cell line, the most used model for in vitro studies of Leydigioma, because it overexpresses CYP19 and constitutively produces high levels of IGF-1 and E2, as well as human LCT. R2C and pediatric LCT angiogenic capability was evaluated in vitro by measuring proliferation of human umbilical vein endothelial cells (HUVEC). In addition, we verified R2C cells angiogenic capability in vivo, using quail embryo vasculature (chorioallantoic membrane assay). Both models have been validated for the study of angiogenesis. Conditioned medium obtained from R2C cell culture stimulated angiogenesis in vitro (p <0.001) as well as in vivo (p <0.001). The in vitro effect was reverted with a previous treatment on the R2C cell culture using α-methyl-DL-histidine hydrochloride (α-MHD, 10 µM), a specific HDC activity inhibitor (p <0.001). Finally, human conditioned medium from pediatric LCT increased HUVEC proliferation (p <0.01). In the same way, the analyzed patients showed higher testosterone and estradiol levels than normal serum concentrations, which was in concordance to phenotypical features observed in presence of LCT. Our results indicate that tumoral Leydig cells (TLC) produce HA, as well as other angiogenic factors, and it could be stimulating the vascular endothelium. The selective inhibition of HDC attenuates the pro-angiogenic capability in TLC. Considering all these results and previous observations of our laboratory, specific inhibitors of HDC could be used, in the future, as a potential therapeutic target for the treatment of LCT.

Color stability of a resin composite: Effect of the immersion method and surface treatments.

Background: In vitro staining methods expose the entire specimen to staining solutions. In a real clinical situation, this is not observed, since one should consider that the bonded surface is not exposed to the oral environment. Theoretically, the clinical condition would be the best simulated if the specimens were exposed to staining solutions by partial immersion. Aims: To evaluate if different immersion methods and surface treatments influence the color stability of resin‑based specimens. Methodology: A stainless steel matrix was used to prepare 30 disc‑shaped specimens that were randomly allocated in three groups: Without polishing, polishing with abrasive discs, and surface sealant. Half of the specimens were isolated to maintain only the upper surface exposed to staining (partial immersion) and the other half was totally immersed in coffee solution for 48 h (total immersion). The coordinates ΔE*, ΔL*, Δa*, Δb* were assessed by spectrophotometer. Statistical Analysis: Two‑way ANOVA and Tukey’s post hoc tests (α =0.05). Results: Specimens submitted to partial immersion showed lower values of ΔE*, ΔL*, Δa*, Δb*, in comparison to total immersion (P = 0.000). Specimens covered by a surface sealant presented lower ΔE* values regardless of the immersion method. Conclusions: Specimens totally immersed in staining solutions could in somehow overestimate the color change, once that in most clinical conditions not all of the restoration surfaces are exposed to the oral environment. Moreover, as the surface sealant application produces color change values that are clinically acceptable, it might be used in esthetic restorations as an adjunct treatment.

Hernia hiatal volvulada no complicada: ¿se debe operar siempre para prevenir la emergencia por isquemia gástrica? / Noncomplicated volvulada hiatal hernia: one is due to always operate to prevent the emergencia by gastric ischemia?

Antecedentes: El estómago herniado en el tórax con componente paraesofágico tiene riesgo de volvulación. Se ha propuesto que el diagnóstico de hernia para esofágica o mixta indica la cirugía electiva para evitar la urgencia; otros opinan que la urgencia sería tan excepcional que no merece dicha consideración. Objetivos: Evaluar la indicación de cirugía en las hernias hiatales mixtas (HHM). Lugar: Departamento de Cirugía, Hospital de Clínicas "José de San Martín", Universidad de Buenos Aires. Diseño: Estudio retrospectivo. Población: 60 pacientes con HHM al diagnóstico (2002-05). Método: Se analiza cuántas estaban volvuadas al momento del diagnóstico por radiología y endoscopia, y en la indicación quirúrgica. Resultados: Sobre 60 pacientes con diagnóstico de HHM, en 18 se observó volvulación gástrica al momento del diagnóstico. 7 (11,6%) pacientes requirieron internación de urgencia: 5 por afagia (2 Nissen laparoscópico, 1 Nissen convencional, 1 Toupet laparoscópico, 1 reducción y cierre defecto diafragmático laparoscópico) y 2 por falla multiorgánica por necrosis gastrica (1 gastrect total, y 1 -93años- no operada). Otros 8 (13%) requirieron adelantar la cirugía programada por agravamiento del dolor, disfagia, anemia y/o regurgitación. Conclusión: El grado de compromiso de la vasculatura o de la luz gastro-esofágica determinará la urgencia quirúrgica, aunque estas alteraciones son dinámicas. Un 25 de los pacientes en esta serie necesitaron acelerar su tratamiento quirúrgico, un 11,6% con internación de urgencia (3,3% con necrosis gástrica).