Tiroiditis subaguda posterior a la administración de la vacuna COVID-19. Presentación de tres casos clínicos / Subacute thyroiditis following COVID-19 vaccine administration. Presentation of three clinical cases

La tiroiditis subaguda (TSA) es un trastorno inflamatorio autolimitado de la glándula tiroides. Es más común en mujeres y se caracteriza por dolor cervical, síntomas inflamatorios sistémicos y disfunción tiroidea. La TSA se ha asociado a una infección viral previa, generalmente respiratoria o enteral. Múltiples virus se han relacionado con TSA. Desde mayo de 2020 se reportaron casos de TSA relacionados con la infección por SARS-CoV-2. Describimos 3 casos de SAT después de la vacuna COVID-19. Dos casos fueron inoculados con vacuna SARS-CoV-2 inactivada (CoronaVac) y uno con vacuna de ARNm Pfizer-BioNTech. Los síntomas clínicos comenzaron pocas semanas después de la inoculación. Presentaron dolor cervical anterior, fiebre, astenia y tirotoxicosis transitoria. En todos los casos la evolución fue favorable. Hasta donde sabemos, estos son los primeros casos de SAT posteriores a la vacuna COVID-19 descritos en Chile.

Subacute thyroiditis (SAT) is a self-limited inflammatory disorder of the thyroid gland. The disease is more common in women and is characterized by neck pain, systemic symptoms, and thyroid dysfunction. SAT It has been associated with viral, respiratory or enteral infection. Multiple viruses had been related to SAT. Since May 2020, cases of SAT related to SARS-CoV-2 infection were reported. We describe 3 cases of SAT following COVID-19 vaccine. Two cases were inoculated with inactivated SARS-CoV-2 vaccine (CoronaVac) and one with mRNA vaccine Pfizer­BioNTech. The clinical symptoms began few weeks after inoculation. They presented with neck pain, fever, general malaise and transient thyrotoxicosis. All cases revered spontaneously. To our knowledge, these are the first cases of SAT following COVID-19 vaccine described in Chile.

ACVR1 R206H cooperates with H3.1K27M in promoting diffuse intrinsic pontine glioma pathogenesis.

Diffuse intrinsic pontine glioma (DIPG) is an incurable pediatric brain tumor, with approximately 25% of DIPGs harboring activating ACVR1 mutations that commonly co-associate with H3.1K27M mutations. Here we show that in vitro expression of ACVR1 R206H with and without H3.1K27M upregulates mesenchymal markers and activates Stat3 signaling. In vivo expression of ACVR1 R206H or G328V with H3.1K27M and p53 deletion induces glioma-like lesions but is not sufficient for full gliomagenesis. However, in combination with PDGFA signaling, ACVR1 R206H and H3.1K27M significantly decrease survival and increase tumor incidence. Treatment of ACVR1 R206H mutant DIPGs with exogenous Noggin or the ACVR1 inhibitor LDN212854 significantly prolongs survival, with human ACVR1 mutant DIPG cell lines also being sensitive to LDN212854 treatment. Together, our results demonstrate that ACVR1 R206H and H3.1K27M promote tumor initiation, accelerate gliomagenesis, promote a mesenchymal profile partly due to Stat3 activation, and identify LDN212854 as a promising compound to treat DIPG.

La anatomía comparada del corazón, una necesidad de práctica de laboratorio en la carrera de medicina / The comparative anatomy of the heart, a need for laboratory practice in the medical career

Introducción: en este curso inició el Plan D para la carrera Medicina, y estando inmersos en la preparación de las nuevas asignaturas rectoras que incluidas anteriormente en Morfofisiología, se propone una práctica de laboratorio con métodos de anatomía comparada. Objetivo: proponer la implementación de una práctica de laboratorio sobre la Anatomía del corazón para el segundo año de medicina, basada en métodos de anatomía comparada. Método: se realizó un estudio cuasiexperimental en la Filial de Ciencias Médicas Manuel Piti Fajardo durante los cursos 2015-16 y 2016-17. Donde se impartió la actividad propuesta al total de estudiantes (104) realizándose la observación de un corazón real de cerdo en comparación con el humano, mostrando aspectos de la anatomía externa e interna, y usando la guía de estudio de la anatomía cardiaca mediante la disección de un corazón porcino. Se aplicaron métodos teóricos: histórico lógico, analítico-sintético, inductivo-deductivo; de los empíricos se aplicó la observación, el análisis de documentos y la técnica del PNI. Resultados: los resultados de la evaluación sistemática fueron comparados con los alcanzados por los 128 estudiantes del curso anterior, encontrándose diferencias significativas entre ellas, se amplió el porcentaje de calificaciones con calidad, se disminuyó ligeramente el porcentaje de calificados de regular y disminuyó el porcentaje de suspensos. Conclusiones: los resultados han sido superiores con la introducción de esta práctica por lo que se propone como parte del programa de la asignatura "Sistemas cardiovascular, respiratorio, digestivo y renal", Plan D, segundo año, Medicina

Introduction: A Lab Practice is proposed to give an answer to methodological problems dealing with a new Curriculum of the Medical Career called Plan D in Medicine Career. It took place in Manuel Piti Fajardo Medical School in San Cristóbal during 2015-2016 and 2016-2017academic courses, is related to a new subject called Cardiovascular, Respiratory, Digestive and Renal systems which were taught before with the name of Morph-physiology. Objective: to offer a suggestion for a lab practice where students have to get familiar to the cardiovascular system using a pig's heart to observe its internal and external characteristics comparing it with a human heart. Methods: it consists of a quasi-experimental study based on a Lab Practice where students have to use a pig's heart to observe its internal and external characteristics comparing it with a human heart. Theoretical methods such us Inductive-Deductive method, Analytic- Synthetic method, Historical - Logical method were used and some empirical methods like observation, documentary analysis and P.N.I. were applied too. The methodology used for carrying out the study is similar to the one used by Biology students in the University of Havana. Results: Systematic evaluation results are presented comparing them, with the ones done before. The initial and final diagnoses are shown. Conclusion: the suggestion is made to work with the plan D curriculum, improving medical students' knowledge, related to a new subjecting Medicine Career called Cardiovascular, Respiratory, Digestive and Renal systems which were taught before with the name of Morph-physiology(AU)

Histone H3.3K27M Represses p16 to Accelerate Gliomagenesis in a Murine Model of DIPG.

Diffuse intrinsic pontine glioma (DIPG) is a highly aggressive pediatric brainstem tumor genetically distinguished from adult GBM by the high prevalence of the K27M mutation in the histone H3 variant H3.3 (H3F3A). This mutation reprograms the H3K27me3 epigenetic landscape of DIPG by inhibiting the H3K27-specific histone methyltransferase EZH2. This globally reduces H3K27me2/3, critical repressive marks responsible for cell fate decisions, and also causes focal gain of H3K27me3 throughout the epigenome. To date, the tumor-driving effects of H3.3K27M remain largely unknown. Here, it is demonstrated that H3.3K27M cooperates with PDGF-B in vivo, enhancing gliomagenesis and reducing survival of p53 wild-type (WT) and knockout murine models of DIPG. H3.3K27M expression drives increased proliferation of tumor-derived murine neurospheres, suggesting that cell-cycle deregulation contributes to increased malignancy in mutant tumors. RNA sequencing on tumor tissue from H3.3K27M-expressing mice indicated global upregulation of PRC2 target genes, and a subset of newly repressed genes enriched in regulators of development and cell proliferation. Strikingly, H3.3K27M induced targeted repression of the p16/ink4a (CDKN2A) locus, a critical regulator of the G0-G1 to S-phase transition. Increased levels of H3K27me3 were observed at the p16 promoter; however, pharmacologic reduction of methylation at this promoter did not rescue p16 expression. Although DNA methylation is also present at this promoter, it is not K27M dependent. Intriguingly, inhibition of DNA methylation restores p16 levels and is cytotoxic against murine tumor cells. Importantly, these data reveal that H3.3K27M-mediated p16 repression is an important mechanism underlying the proliferation of H3.3K27M tumor cells, as in vivo cdkn2a knockout eliminates the survival difference between H3.3K27M and H3.3WT tumor-bearing mice.Implications: This study shows that H3.3K27M mutation and PDGF signaling act in concert to accelerate gliomagenesis in a genetic mouse model and identifies repression of p16 tumor suppressor as a target of H3.3K27M, highlighting the G1-S cell-cycle transition as a promising therapeutic avenue. Mol Cancer Res; 15(9); 1243-54. ©2017 AACR.

Caracterización de pacientes controlados por enfermedad de Basedow Graves en un hospital universitario / Clinical features of patients with Basedow Graves disease seen at a university hospital

Background: Basedow Graves disease (BGD) is the leading cause of hyperthyroidism. The characteristics of patients seen at a university hospital may differ from those described in the general population. Aim: To describe the clinical features of patients with BGD seen at a university hospital. Material and Methods: Review of medical records of all patients seen at our hospital between 2009 and 2014 with the diagnosis of thyrotoxicosis, hyperthyroidism or BGD. Clinical features, laboratory results and treatments were recorded. Results: We reviewed clinical records of 272 patients; 15 had to be excluded due to incomplete data. BGD was present in 77.9% (n = 212). The mean age of the latter was 42 years (range 10-81) and 76% were women. Ninety six percent were hyperthyroid at diagnosis and thyroid stimulating hormone was below 0.1 mIU/L in all patients. Median free thyroxin and triiodothyronine levels were 3.26 ng/dl and 3.16 ng/ml, respectively. Thyrotropin-receptor antibodies were positive in 98.5% and 85.7% had positive thyroid peroxidase antibodies. Graves orbitopathy (GO) was clinically present in 55% of patients. Of this group, 47% had an active GO, 26% had a moderate to severe disease and 7.8% had sight-threatening GO. As treatment, 26% received radioiodine, 44% anti-thyroid drugs exclusively, 28% underwent thyroidectomy and 2% did not require therapy. Conclusions: In this group of patients, we observed a greater frequency of severe eye disease and a high rate of surgical management. This finding could be explained by referral to highly qualified surgical and ophthalmological teams.

Determinación de niveles de vitamina D en pacientes con fibromialgia: estudio de casos y controles / Vitamin D levels in patients with fibromyalgia: case control study

Introduction: fibromyalgia (FM) is characterized by diffuse chronic muscle pain, fatigue and disability, affecting quality of life. In recent years there are many reports that show a high prevalence of vitamin D deficiency in different populations. In patients with FM there are conflicting results about the associations with vitamin D deficiency. Method: Case control study matched controls by age and sex. A clinical interview, measurement of 25-OH vitamin D, calcium, phosphorus and intact PTH was measured. The definitions of the American Society of Endocrinology were used: Insufficient vitamin D levels of 21-29 ng/ml and deficiency when they are less than 20 ng/ml. Results: 39 female patients were included in each group. The average age was 46.33 years (SD 10.6) in patients with FM and 45.92 years (SD 11.9) in controls. VD average levels in women with FM was 26.13 ng/ml (SD 8.3) and the controls of 28.45 ng/ml (SD 8.7) p = 0.082. No group differences were found when using cutoffs of 30 ng/dl (OR 2.75 with p = 0.35 [95 percent CI 0.96 to 8.06]) or 20 ng/dl (OR 0,6 p = 0.38 [95 percent CI 0.15 to 2.18]). No VD patients with levels below 10 ng/dl were presented. Conclusions: We found no differences between groups in VD levels when considering the average levels of VD or using different cutoffs.

Tumor location, but not H3.3K27M, significantly influences the blood-brain-barrier permeability in a genetic mouse model of pediatric high-grade glioma.

Pediatric high-grade gliomas (pHGGs) occur with strikingly different frequencies in infratentorial and supratentorial regions. Although histologically these malignancies appear similar, they represent distinct diseases. Recent genomic studies have identified histone K27M H3.3/H3.1 mutations in the majority of brainstem pHGGs; these mutations are rarely encountered in pHGGs that arise in the cerebral cortex. Previous research in brainstem pHGGs suggests a restricted permeability of the blood-brain-barrier (BBB). In this work, we use dynamic contrast-enhanced (DCE) MRI to evaluate BBB permeability in a genetic mouse model of pHGG as a function of location (cortex vs. brainstem, n = 8 mice/group) and histone mutation (mutant H3.3K27M vs. wild-type H3.3, n = 8 mice/group). The pHGG models are induced either in the brainstem or the cerebral cortex and are driven by PDGF signaling and p53 loss with either H3.3K27M or wild-type H3.3. T2-weighted MRI was used to determine tumor location/extent followed by 4D DCE-MRI for estimating the rate constant (K (trans) ) for tracer exchange across the barrier. BBB permeability was 67 % higher in cortical pHGGs relative to brainstem pHGGs (t test, p = 0.012) but was not significantly affected by the expression of mutant H3.3K27M versus wild-type H3.3 (t-test, p = 0.78). Although mice became symptomatic at approximately the same time, the mean volume of cortical tumors was 3.6 times higher than the mean volume of brainstem tumors. The difference between the mean volume of gliomas with wild-type and mutant H3.3 was insignificant. Mean K (trans) was significantly correlated to glioma volume. These results present a possible explanation for the poor response of brainstem pHGGs to systemic therapy. Our findings illustrate a potential role played by the microenvironment in shaping tumor growth and BBB permeability.

Factores de crecimiento aportados por el lisado plaquetario en el tratamiento tópico de úlceras posflebíticas / Platelet lysate-derived growth factors for topical treatment of postphlebitis ulcers

Introducción: los factores de crecimiento plaquetario son proteínas bioactivas que se sintetizan y almacenan en las plaquetas. Objetivo: evaluar la efectividad de los factores de crecimiento aportados por el lisado plaquetario alogénico en el tratamiento tópico de úlceras posflebíticas Métodos: se realizó un estudio cuasi-experimental con control simultáneo en la consulta de medicina regenerativa, Hospital General Docente "Comandante Pinares", entre enero de 2008 y diciembre de 2012. Se evaluaron 135 pacientes con el diagnóstico de úlceras posflebíticas con inadecuada respuesta al tratamiento convencional y ausencia de otras enfermedades de base que impidieran una respuesta a la terapia regenerativa. Los pacientes se dividieron en dos grupos: 90 recibieron tratamiento con la aplicación local del lisado plaquetario obtenido de las plaquetas alogénicas ABO compatibles y 45 mantuvieron el tratamiento convencional (grupo control). El tiempo de respuesta fue la característica distintiva para medir la eficacia entre ambos tratamientos. Resultados: predominó el sexo femenino y edad de más de 50 años. Los síntomas cardinales del síndrome posflebítico, estuvieron presentes en un mayor número de pacientes del grupo tratado con el lisado plaquetario, sin embargo, a los 30 días, se constató una mejoría de los mismos así como una disminución significativa del área promedio de las úlceras. En el grupo tratado con lisado, 86 pacientes remitieron sus síntomas en menos de seis semanas, frente a solo ocho en el mismo tiempo en el grupo convencional. Conclusiones: el uso de factores de crecimiento aportados por el lisado plaquetario alogénico fue efectivo en el tratamiento tópico de úlceras posflebíticas(AU)

Introduction: platelet-derived growth factors are bio-active proteins that are synthesized and stored in the platelets. Objective: to evaluate the effectiveness of allogenic platelet lysate-derived growth factors in the topical treatment of postphlebitis ulcers. Methods: a quasi-experimental study with simultaneous control was conducted from January 2008 through December 2012 in the regenerative medicine service of "Comandante Pinares" general teaching hospital located in San Cristobal, Artemisa province, Cuba. One hundred and thirty five patients with diagnosis of postphlebitis ulcers, inadequate response to the conventional treatment and absence of other illnesses that could hinder such response to regenerative therapy were evaluated. The patients were divided into two groups: 90 treated with local use of compatible ABO allogenic platelet-derived platelet lysate and 45 kept under the conventional treatment (control group). The reaction time was the distinctive characteristic to measure the effectiveness of both treatments. Results: females and over 50 years-old age predominated. The main symptoms of the posphlebitic syndrome were present in a high number of patients in the group treated with the platelet lysate. Thirty days later, these symptoms significantly improved and the average ulcer area dramatically decreased. There was observed symptoms remission in eighty six patients in less than six weeks in contrast with only eight in the conventional group during this period. Conclusions: the use of allogenic platelet lysate-derived growth factors was effective in the topical treatment of postphlebitis ulcers(AU)

Pre-Clinical Models of Diffuse Intrinsic Pontine Glioma.

Diffuse intrinsic pontine glioma (DIPG) is a rare and incurable brain tumor that arises in the brainstem of children predominantly between the ages of 6 and 8. Its intricate morphology and involvement of normal pons tissue precludes surgical resection, and the standard of care today remains fractionated radiation alone. In the past 30 years, there have been no significant advances made in the treatment of DIPG. This is largely because we lack good models of DIPG and therefore have little biological basis for treatment. In recent years, however, due to increased biopsy and acquisition of autopsy specimens, research is beginning to unravel the genetic and epigenetic drivers of DIPG. Insight gleaned from these studies has led to improvements in approaches to both model these tumors in the lab and to potentially treat them in the clinic. This review will detail the initial strides toward modeling DIPG in animals, which included allograft and xenograft rodent models using non-DIPG glioma cells. Important advances in the field came with the development of in vitro cell and in vivo xenograft models derived directly from autopsy material of DIPG patients or from human embryonic stem cells. Finally, we will summarize the progress made in the development of genetically engineered mouse models of DIPG. Cooperation of studies incorporating all of these modeling systems to both investigate the unique mechanisms of gliomagenesis in the brainstem and to test potential novel therapeutic agents in a preclinical setting will result in improvement in treatments for DIPG patients.

A high-throughput in vitro drug screen in a genetically engineered mouse model of diffuse intrinsic pontine glioma identifies BMS-754807 as a promising therapeutic agent.

Diffuse intrinsic pontine gliomas (DIPGs) represent a particularly lethal type of pediatric brain cancer with no effective therapeutic options. Our laboratory has previously reported the development of genetically engineered DIPG mouse models using the RCAS/tv-a system, including a model driven by PDGF-B, H3.3K27M, and p53 loss. These models can serve as a platform in which to test novel therapeutics prior to the initiation of human clinical trials. In this study, an in vitro high-throughput drug screen as part of the DIPG preclinical consortium using cell-lines derived from our DIPG models identified BMS-754807 as a drug of interest in DIPG. BMS-754807 is a potent and reversible small molecule multi-kinase inhibitor with many targets including IGF-1R, IR, MET, TRKA, TRKB, AURKA, AURKB. In vitro evaluation showed significant cytotoxic effects with an IC50 of 0.13 µM, significant inhibition of proliferation at a concentration of 1.5 µM, as well as inhibition of AKT activation. Interestingly, IGF-1R signaling was absent in serum-free cultures from the PDGF-B; H3.3K27M; p53 deficient model suggesting that the antitumor activity of BMS-754807 in this model is independent of IGF-1R. In vivo, systemic administration of BMS-754807 to DIPG-bearing mice did not prolong survival. Pharmacokinetic analysis demonstrated that tumor tissue drug concentrations of BMS-754807 were well below the identified IC50, suggesting that inadequate drug delivery may limit in vivo efficacy. In summary, an unbiased in vitro drug screen identified BMS-754807 as a potential therapeutic agent in DIPG, but BMS-754807 treatment in vivo by systemic delivery did not significantly prolong survival of DIPG-bearing mice.

Lisado plaquetario alogénico en la necrosis del colgajo / Alogenic platelet lysate in necrosis of the torn piece

La utilización de lisado plaquetario alogénico abre otra posibilidad terapéutica en ortopedia. Se presenta su uso en una paciente femenina de 40 años de edad, con antecedentes de asma bronquial y tratamiento con esteroides, que como consecuencia de una caída sufrió herida avulsiva extensa en el tercio inferior de la pierna derecha con desgarro de piel de aproximadamente 11 cm con vértice distal y base proximal estrecha, que solamente tomó piel; y otra herida similar, aledaña a esta lesión, de aproximadamente 6 cm de diámetro. Se le realizó toilette y necreptomía de los bordes que tenían signos de necrosis, fundamentalmente los vértices. Se le realizaron puntos de afrontamiento donde se observó extrema fragilidad de la piel, se inició tratamiento con antibióticoterapia. A las 48 horas se observó necrosis de dos tercios del colgajo de piel, el cual se decidió mantener hasta pasados 10 días. Cuando se le retiró se comenzó a usar lisado plaquetario local en curaciones en días alternos. Se observó mejoría de la granulación, no así de la piel aledaña a la lesión. Posteriormente se le realizó infiltración perilesional con lisado plaquetario alogénico, con cuyo proceder mejoró el aspecto de la lesión y la cicatrización en un período de solo 7 días...

The use of allogenic platelet lysate opens another therapeutic possibility in orthopedics. Its use is presented in a 40 year-old patient with previous history of bronchial asthma and treated with steroids who, as a result a fall, suffered an extensive avulsive wound in her right foot of approximately 11 cm with skin laceration and necrosis of the torn piece, with vertex distal and proximal base that only took skin, with another torn piece of similar bodering and a diameter of approximatety 6 cm. A toilette and necrectomy of the cyanotic edge was made, mainly in the vertexes. Confrontation stitches were taken and an extreme fragility of the skin was observed when carrying this procedure. Treatment with antibiotics was started and after 48 hours necrosis of two third of the skin of the torn piece was observed which was not removed for ten days. After removal local therapy with alogenic platelet lysate was applied on alternate days. Improving of granulation was observed, but not in the surrounding skin lesion. Then, a perilessional infiltration with allogenic platelet lysate was made which improved the lesion appearance and its healing in a period of only 7 days...

Genomic analysis of diffuse intrinsic pontine gliomas identifies three molecular subgroups and recurrent activating ACVR1 mutations.

Diffuse intrinsic pontine glioma (DIPG) is a fatal brain cancer that arises in the brainstem of children, with no effective treatment and near 100% fatality. The failure of most therapies can be attributed to the delicate location of these tumors and to the selection of therapies on the basis of assumptions that DIPGs are molecularly similar to adult disease. Recent studies have unraveled the unique genetic makeup of this brain cancer, with nearly 80% found to harbor a p.Lys27Met histone H3.3 or p.Lys27Met histone H3.1 alteration. However, DIPGs are still thought of as one disease, with limited understanding of the genetic drivers of these tumors. To understand what drives DIPGs, we integrated whole-genome sequencing with methylation, expression and copy number profiling, discovering that DIPGs comprise three molecularly distinct subgroups (H3-K27M, silent and MYCN) and uncovering a new recurrent activating mutation affecting the activin receptor gene ACVR1 in 20% of DIPGs. Mutations in ACVR1 were constitutively activating, leading to SMAD phosphorylation and increased expression of the downstream activin signaling targets ID1 and ID2. Our results highlight distinct molecular subgroups and novel therapeutic targets for this incurable pediatric cancer.

PD-0332991, a CDK4/6 inhibitor, significantly prolongs survival in a genetically engineered mouse model of brainstem glioma.

Diffuse intrinsic pontine glioma (DIPG) is an incurable tumor that arises in the brainstem of children. To date there is not a single approved drug to effectively treat these tumors and thus novel therapies are desperately needed. Recent studies suggest that a significant fraction of these tumors contain alterations in cell cycle regulatory genes including amplification of the D-type cyclins and CDK4/6, and less commonly, loss of Ink4a-ARF leading to aberrant cell proliferation. In this study, we evaluated the therapeutic approach of targeting the cyclin-CDK-Retinoblastoma (Rb) pathway in a genetically engineered PDGF-B-driven brainstem glioma (BSG) mouse model. We found that PD-0332991 (PD), a CDK4/6 inhibitor, induces cell-cycle arrest in our PDGF-B; Ink4a-ARF deficient model both in vitro and in vivo. By contrast, the PDGF-B; p53 deficient model was mostly resistant to treatment with PD. We noted that a 7-day treatment course with PD significantly prolonged survival by 12% in the PDGF-B; Ink4a-ARF deficient BSG model. Furthermore, a single dose of 10 Gy radiation therapy (RT) followed by 7 days of treatment with PD increased the survival by 19% in comparison to RT alone. These findings provide the rationale for evaluating PD in children with Ink4a-ARF deficient gliomas.

Impacto del tratamiento con células madre adultas en la osteoartrosis de la rodilla / Impact of the treatment with adult stem cells in knee osteoarthrosis

Introducción: la osteoartrosis de la rodilla (OAR) es la causa más frecuente de artritis en la población por encima de los 55 años de edad. A menudo se asocia con discapacidad y deterioro variable de la calidad de vida. En la actualidad, el tratamiento con células madre ha abierto una alternativa más dentro del arsenal terapéutico con que se cuenta. Objetivo: evaluar la eficacia y seguridad del autotrasplante de células madre adultas en el tratamiento de la osteoartrosis de rodilla. Métodos: se realizó un estudio desde mayo 2009 hasta diciembre 2011, en el que se incluyeron 123 pacientes adultos con OAR atendidos en la consulta de medicina regenerativa, que no respondían a los tratamientos convencionales. Se les realizó el implante intrarticular de células mononucleares de sangre periférica (CMN-SP) autólogas, movilizadas mediante el factor estimulante de colonias granulocíticas. En todos los casos prevalecía el dolor y la dificultad a la marcha al inicio del tratamiento. Resultados: a los seis meses se observó mejoría clínica y radiológica en 117 pacientes (95,1 por ciento) y solo en seis enfermos (4,9 por ciento) no hubo la respuesta deseada, coincidiendo estos con los que presentaron trastornos de alineación marcados, en los cuales el dolor no desapareció, pero sí existió modificación de la intensidad. Conclusiones: el implante de CMN-SP es un método factible, simple, seguro y menos costoso para el tratamiento de OAR. Se recomienda que si existe deformidad angular acentuada marcada, esta debe corregirse antes del implante para que el proceder sea exitoso

Introduction: osteoarthrosis an every day more frequent degenerative disease affecting the quality of life of people over 55 years old and its treatment is a great challenge. The use of stem cells has open a new alternative in the available therapeutic arsenal. Objective: to assess the efficacy and safety of autologous adult stem cell transplantation in the treatment of knee osteoarthrosis. Methods: the study took place from May 2009 to December 2011 in 123 adult patients with OAR from the regenerative medicine outpatient service who had no response to conventional treatments. Intra-articular implantation of autologous peripheral blood mononuclear cells (MNC-SP) mobilized by granulocyte colony stimulating factor was performed. In all cases pain and gait difficulty at baseline prevailed. Results: after six months, clinical and radiological improvement in 117 patients (95,1 percent) were observed and only in six patients (4,9 percent) the expected response was not obtained. These last patients presented marked alignment disorders and the pain did not disappear, but there was a positive change in its intensity. Conclusions: the CMN-SP implant is a feasible, simple, safe and less expensive method for the treatment of knee osteoarthrosis. It is recommended that in cases with marked angular deformity, this disorder should be corrected prior to MNC-SP implantation so the procedure be successful

Inhibition of PRC2 activity by a gain-of-function H3 mutation found in pediatric glioblastoma.

Sequencing of pediatric gliomas has identified missense mutations Lys27Met (K27M) and Gly34Arg/Val (G34R/V) in genes encoding histone H3.3 (H3F3A) and H3.1 (HIST3H1B). We report that human diffuse intrinsic pontine gliomas (DIPGs) containing the K27M mutation display significantly lower overall amounts of H3 with trimethylated lysine 27 (H3K27me3) and that histone H3K27M transgenes are sufficient to reduce the amounts of H3K27me3 in vitro and in vivo. We find that H3K27M inhibits the enzymatic activity of the Polycomb repressive complex 2 through interaction with the EZH2 subunit. In addition, transgenes containing lysine-to-methionine substitutions at other known methylated lysines (H3K9 and H3K36) are sufficient to cause specific reduction in methylation through inhibition of SET-domain enzymes. We propose that K-to-M substitutions may represent a mechanism to alter epigenetic states in a variety of pathologies.

Aplicación local de lisado plaquetario en úlceras posflebíticas / Local application of platelet lysate on posflebitic ulcers

El tratamiento de las úlceras postrombóticas o posflebíticas constituye un reto para la medicina debido a su cronicidad y a sus frecuentes recidivas que condicionan múltiples trastornos locales y sistémicos, con una mala calidad de vida del paciente. En este trabajo se incluyeron 80 pacientes con úlceras posflebíticas en miembros inferiores que fueron divididos en 2 grupos: 40 tratados con lisados de plaquetas alogénicas conservadas y 40 tratados convencionalmente, que conformaron el grupo control. Se consideró como buen resultado cuando a los 30 días de tratamiento o antes, el paciente presentó una respuesta parcial o total. En el 95 por ciento de los enfermos tratados con el lisado se obtuvo una buena respuesta (suma de las totales y parciales) contra el 75 por ciento en el grupo control (p>0,001). El uso del lisado plaquetario resultó un proceder simple y efectivo en el tratamiento de úlceras posflebíticas en miembros inferiores, que puede ser recomendado, ya que los pacientes pueden mantenerse en sus hogares y así se elimina el costo hospitalario que generalmente tiene el tratamiento de este tipo de lesión

Treatment of post-thrombotic ulcers or postflebitic is a challenge to medicine because of its chronicity and frequent recurrences that determine multiple local and systemic disorders with poor quality of life for patients. This study included 80 patients with lower limb posflebitic ulcers, who were grouped into 2 groups: 40 treated with preserved allogeneic platelet lysates and 40 were treated conventionally. The latter was the control group. It was considered good result when the patient had a partial or complete response after 30 days of treatment or before. Good response was found in 95 percent of patients treated with lysate (sum of total and partial values) versus 75 percent in the control group (p> 0.001). The use of platelet lysate was a simple and effective procedure in the treatment of lower limb posflebitic ulcers. This treatment can be recommended, since patients can stay at home, thus eliminating the hospital costs incurred in this type of treatment

Distribution of pesticides and PCBs in sediments of agricultural drains in the Culiacan Valley, Sinaloa, Mexico.

Agriculture is one of the most important economic activities in Sinaloa, Mexico. The Culiacan Valley is an extensive agricultural region characterized by a variety of crops with high-yield productions. In this study, concentrations of organochlorine (OCPs) and organophosphorus (OPs) pesticides and polychlorobiphenyls (PCBs) were determined in sediments of the agricultural drainage system of Culiacan Valley. Overall, 32 compounds were detected, with concentrations widely ranging from 0.03 to 1 294 ng g(-1) dry weight. OCP concentrations (15) ranged from 0.1 to 20.19 ng g(-1) dw. OP concentrations (8) ranged from 0.03 to 1294 ng g(-1) dw, and diazinon was the compound with the highest concentration. PCB concentrations were also determined and varied from 0.05 to 3.29 ng g(-1) dw. Other compounds detected included permethrin, triadimefon, and fipronil. The central zone registered the higher concentrations and the greatest number of compounds, which could be related to the occurrence of horticultural fields in this zone. According to sediment quality guidelines, the compounds exceeding the probable effect level were γ-HCH, p,p'-DDT and p,p'-DDE, while the pesticides above the maximum permissible concentration were endosulfan, azinphos methyl, diazinon, dichlorvos, and permethrin. Although Sinaloa is an important agricultural crop producer in northwest Mexico, there are not many studies dealing with pesticide distribution in agricultural areas.

Terapia celular en fractura del fémur / Cell therapy in femur fractures

La medicina regenerativa ha abierto una posibilidad más para la consolidación efectiva y la recuperación rápida de los pacientes con lesiones traumáticas. Se presenta un paciente masculino, blanco, de 46 años de edad con antecedentes de accidente de tránsito. Se diagnosticó fractura del tercio medio del fémur izquierdo y las radiografías simples evidenciaron conminución Grado IV. Egresó después de 20 días de internamiento con persistencia del dolor a pesar de habérsele administrado analgésicos cada 4-6 horas. Se indicó terapia celular que se realizó en régimen ambulatorio. A partir de las primeras 48 horas la mejoría se incrementó progresivamente, logró estabilidad y desapareció el dolor en el foco de fractura, síntoma que mantenía desde el accidente. A las 8 semanas después de la terapia celular se observó mejoría radiológica. En general, su evolución se consideró satisfactoria por la pronta mejoría y su incorporación a la vida social. Este es el primer paciente en la provincia de Artemisa en que se ha realizado este nuevo tipo de terapia y hasta donde conocemos en el momento de la redacción de este trabajo, también el primero informado en la literatura científica en Cuba

Regenerative medicine has opened another opportunity for effective consolidation and rapid recovery of patients with traumatic injuries. We present a 46 year- old white male patient with a history of traffic accident. A middle third left femur fracture was diagnosed and plain radiographs showed IV grade comminution. He was released after 20 days of hospitalization with persistent pain despite of pain medication every 4-6 hours. Cell therapy was prescribed and it was performed on outpatient basis. After 48 hours the improvement was increased progressively, stability was achieved and pain disappeared in the fracture site, this was a symptom present since the accident. 8 weeks after cell therapy, radiological improvement was observed. In general, his eveolution was considered satisfactory for the fast recovery and its incorporation into social life. This is the first patient in Artemisa province who underwent this new type of therapy and as far as we know at the time of this writing, it is also the first reported in the scientific literature in Cuba