Epigenetic-based differentiation therapy for Acute Myeloid Leukemia.

Despite the development of novel therapies for acute myeloid leukemia, outcomes remain poor for most patients, and therapeutic improvements are an urgent unmet need. Although treatment regimens promoting differentiation have succeeded in the treatment of acute promyelocytic leukemia, their role in other acute myeloid leukemia subtypes needs to be explored. Here we identify and characterize two lysine deacetylase inhibitors, CM-444 and CM-1758, exhibiting the capacity to promote myeloid differentiation in all acute myeloid leukemia subtypes at low non-cytotoxic doses, unlike other commercial histone deacetylase inhibitors. Analyzing the acetylome after CM-444 and CM-1758 treatment reveals modulation of non-histone proteins involved in the enhancer-promoter chromatin regulatory complex, including bromodomain proteins. This acetylation is essential for enhancing the expression of key transcription factors directly involved in the differentiation therapy induced by CM-444/CM-1758 in acute myeloid leukemia. In summary, these compounds may represent effective differentiation-based therapeutic agents across acute myeloid leukemia subtypes with a potential mechanism for the treatment of acute myeloid leukemia.

Uso del sildenafilo oral en el tratamiento del linfangioma orbitario / Use of Oral Sildenafil in the Treatment of Orbital Lymphangioma

Los linfangiomas orbitarios son malformaciones vasculares benignas, de crecimiento lento, abortivas y no funcionales, que se presentan principalmente en la primera década de la vida. Las opciones terapéuticas en estos casos presentan una resolutividad limitada, algunos tratamientos suelen ser agresivos y provocar daños del aparato visual. Se presenta un caso de una paciente femenina de 6 años de edad atendida por proptosis del ojo izquierdo a la que se le realizó el diagnóstico clínico-imagenológico de linfangioma de la órbita, con el objetivo de mostrar el resultado alcanzado en el manejo de la misma mediante el uso del sildenafilo por vía oral, modalidad terapéutica en estudio a nivel mundial en el tratamiento de estas afecciones. El tratamiento con sildenafilo en el linfangioma orbitario demostró ser eficaz en la mejoría del cuadro clínico y por imágenes. Durante el tratamiento no se reportaron reacciones adversas(AU)

Orbital lymphatic malformations are benign, slow-growing, abortive, nonfunctional vascular malformations that occur mainly in the first decade of life. Therapeutic options in these cases present limited resolution, some treatments are usually aggressive and cause damage to the visual apparatus. We present a case of a 6-year-old female patient treated for proptosis of the left eye. The clinical-imaging diagnosis of lymphangioma of the orbit was made to show the results achieved in its treatment through the use of oral sildenafil, a therapeutic modality under study worldwide in the treatment of these conditions. The treatment with sildenafil in orbital lymphangioma proved to be effective in the improvement of the clinical and imaging picture. No adverse reactions were reported during treatment(AU)

Características epidemiológicas, clínicas y oftalmológicas de pacientes con queratoconjuntivitis seca / Epidemiological, clinical and ophthalmologic characteristics of patients with keratoconjunctivitis Sicca

Introducción: La queratoconjuntivitis seca es una enfermedad de causa multifactorial, que afecta la producción de lágrimas y la superficie ocular, a la vez que ocasiona malestar, visión borrosa e inestabilidad de la película lagrimal. Métodos: Se realizó un estudio descriptivo y transversal de 50 pacientes con diagnóstico de queratoconjuntivitis seca, atendidos en el Centro Oftalmológico del Hospital General Docente Dr. Juan Bruno Zayas Alfonso de Santiago de Cuba, desde enero hasta julio de 2020. Objetivo: Caracterizar a los pacientes con queratoconjuntivitis seca según variables epidemiológicas clínicas y oftalmológicas. Resultados: En la serie predominaron las féminas (66,0 %), los pacientes mayores de 60 años (40,0 %), la lectura excesiva como factor de riesgo (42,0 %), la irritación, la fatiga ocular y la visión borrosa como criterios diagnósticos, además de la disminución del tiempo de rotura de la película lagrimal en 68,0 % de la muestra, entre otros resultados. Conclusión: La queratoconjuntivitis seca, desde el punto de vista clínico y epidemiológico fue similar a lo descrito en la bibliografía especializada en cuanto a los grupos de edades, sexo y principales síntomas descritos.

Introduction: The keratoconjunctivitis sicca is a disease of multifactorial cause that affects the production of tears and the ocular surface, at the same time that causes discomfort, blurred vision and instability of the lacrimal thin layer. Methods: A descriptive and cross-sectional study of 50 patients with diagnosis of keratoconjunctivitis sicca, assisted in the Ophthalmolgic Center of Dr. Juan Bruno Zayas Alfonso Teaching General Hospital in Santiago de Cuba, was carried out from January to July, 2020. Objective: To characterize patients with keratoconjunctivitis sicca according to clinical, epidemiologic and ophthalmologic variables. Results: In the series there was a prevalence of the females (66.0 %), patients over 60 years (40.0 %), excessive reading as risk factor (42.0 %), irritation, ocular fatigue and blurred vision as diagnostic criteria, besides the decrease of the lacrimal thin layer break up time in 68.0 % of the sample, among other results. Conclusion: The keratoconjunctivitis sicca was similar to that described in the specialized literature review as for the age groups, sex and main described symptoms from the clinical and epidemiologic points of view.

Local Preirradiation of Infarcted Cardiac Tissue Substantially Enhances Cell Engraftment.

The success of cell therapy for the treatment of myocardial infarction depends on finding novel approaches that can substantially implement the engraftment of the transplanted cells. In order to enhance cell engraftment, most studies have focused on the pretreatment of transplantable cells. Here we have considered an alternative approach that involves the preconditioning of infarcted heart tissue to reduce endogenous cell activity and thus provide an advantage to our exogenous cells. This treatment is routinely used in other tissues such as bone marrow and skeletal muscle to improve cell engraftment, but it has never been taken in cardiac tissue. To avoid long-term cardiotoxicity induced by full heart irradiation we developed a rat model of a catheter-based heart irradiation system to locally impact a delimited region of the infarcted cardiac tissue. As proof of concept, we transferred ZsGreen+ iPSCs in the infarcted heart, due to their ease of use and detection. We found a very significant increase in cell engraftment in preirradiated rats. In this study, we demonstrate for the first time that preconditioning the infarcted cardiac tissue with local irradiation can substantially enhance cell engraftment.

Blefaroplastia: resultados del empleo de dos técnicas en el Centro Oftalmológico de Santiago de Cuba / Blepharoplasty: results of using two techniques in the Ophthalmologic Center from Santiago de Cuba

Introducción: La blefaroplastia produce resultados clínicos y estéticos favorables en los pacientes aquejados por dermatocalasis. Objetivo: Evaluar los resultados de los procedimientos quirúrgicos convencional y con láser de CO2 en estos afectados. Métodos: Se realizó un estudio descriptivo, prospectivo y trasversal de 300 pacientes con dermatocalasis, atendidos en el Servicio de Oculoplastia del Centro Oftalmológico del Hospital General Docente Dr Juan Bruno Zayas Alfonso de Santiago de Cuba, desde enero de 2015 hasta diciembre de 2016. Resultados: Predominaron el grupo etario de 40 a 59 años, el sexo femenino y la afectación en los párpados superiores, sin diferencias significativas en cuanto a las técnicas quirúrgicas empleadas; se observó un mayor número de complicaciones en los pacientes operados de manera convencional, con más frecuencia del sangrado. En general los pacientes evolucionaron satisfactoriamente y los que presentaron limitaciones del campo visual superior se recuperaron sin dificultad luego de la intervención quirúrgica. Conclusiones: La blefaroplastia con láser de CO2 constituye una mejor y más calificada opción terapéutica para la corrección de la dermatocalasis

Introduction: Blepharoplasty produces favorable clinical and cosmetic results in the patients that are suffering from dermatochalasis. Objective: To evaluate the results of the conventional and CO2 laser surgical procedures in these affected patients. Methods: A descriptive, prospective and cross-sectional study of 300 patients with dermatochalasis, assisted in the Oculoplasty Service of Dr Juan Bruno Zayas Alfonso Teaching General Hospital Ophthalmologic Center was carried out in Santiago de Cuba, from January, 2015 to December, 2016. Results: There was a prevalence of the 40 to 59 age group, female sex and upper lids disorder, without significant differences concerning the surgical techniques that were used; a higher number of complications in patients operated with a conventional way was observed, with more frequency of bleeding. In general the patients had a favorable clinical course and those that presented limitations of the upper visual field recovered without difficulty after the surgical intervention. Conclusions: Blepharoplasty with CO2 laser constitutes a better and more qualified therapeutic option for the correction of dermatochalasis

Infiltration of plasma rich in growth factors enhances in vivo angiogenesis and improves reperfusion and tissue remodeling after severe hind limb ischemia.

PRGF is a platelet concentrate within a plasma suspension that forms an in situ-generated fibrin-matrix delivery system, releasing multiple growth factors and other bioactive molecules that play key roles in tissue regeneration. This study was aimed at exploring the angiogenic and myogenic effects of PRGF on in vitro endothelial cells (HUVEC) and skeletal myoblasts (hSkMb) as well as on in vivo mouse subcutaneously implanted matrigel and on limb muscles after a severe ischemia. Human PRGF was prepared and characterized. Both proliferative and anti-apoptotic responses to PRGF were assessed in vitro in HUVEC and hSkMb. In vivo murine matrigel plug assay was conducted to determine the angiogenic capacity of PRGF, whereas in vivo ischemic hind limb model was carried out to demonstrate PRGF-driven vascular and myogenic regeneration. Primary HUVEC and hSkMb incubated with PRGF showed a dose dependent proliferative and anti-apoptotic effect and the PRGF matrigel plugs triggered an early and significant sustained angiogenesis compared with the control group. Moreover, mice treated with PRGF intramuscular infiltrations displayed a substantial reperfusion enhancement at day 28 associated with a fibrotic tissue reduction. These findings suggest that PRGF-induced angiogenesis is functionally effective at expanding the perfusion capacity of the new vasculature and attenuating the endogenous tissue fibrosis after a severe-induced skeletal muscle ischemia.

Functional MMP-10 is required for efficient tissue repair after experimental hind limb ischemia.

We studied the role of matrix metalloproteinase-10 (MMP-10) during skeletal muscle repair after ischemia using a model of femoral artery excision in wild-type (WT) and MMP-10 deficient (Mmp10(-/-)) mice. Functional changes were analyzed by small animal positron emission tomography and tissue morphology by immunohistochemistry. Gene expression and protein analysis were used to study the molecular mechanisms governed by MMP-10 in hypoxia. Early after ischemia, MMP-10 deficiency resulted in delayed tissue reperfusion (10%, P < 0.01) and in increased necrosis (2-fold, P < 0.01), neutrophil (4-fold, P < 0.01), and macrophage (1.5-fold, P < 0.01) infiltration. These differences at early time points resulted in delayed myotube regeneration in Mmp10(-/-) soleus at later stages (regenerating myofibers: 30 ± 9% WT vs. 68 ± 10% Mmp10(-/-), P < 0.01). The injection of MMP-10 into Mmp10(-/-) mice rescued the observed phenotype. A molecular analysis revealed higher levels of Cxcl1 mRNA (10-fold, P < 0.05) and protein (30%) in the ischemic Mmp10(-/-) muscle resulting from a lack of transcriptional inhibition by MMP-10. This was further confirmed using siRNA against MMP-10 in vivo. Our results demonstrate an important role of MMP-10 for proper muscle repair after ischemia, and suggest that chemokine regulation such as Cxcl1 by MMP-10 is involved in muscle regeneration.