Testicular Germ Cell Tumors in Children and Adolescents Treated With Bleomycin, Etoposide, and Cisplatin (BEP) Protocol: A Survival Analysis.

BACKGROUND: Germ cell tumors (GCTs) represent a diverse group of rare neoplasms that vary in location, histology, and clinical presentation. This study focuses on the clinical outcomes and survival rates of children and adolescents treated with the bleomycin, etoposide, and cisplatin (BEP) protocol. METHODS: This observational study evaluated children under 18 years diagnosed with testicular germ cell tumors and treated with the BEP protocol from January 2008 to December 2018. We employed descriptive analysis and used the Kaplan-Meier method to calculate event-free survival (EFS) and overall survival rates. RESULTS: The study included 32 patients with an average age of 9.8 years (SD ± 6.7). The primary reason for consultation was a testicular mass. The classification of patients was E-I for 14 patients (44%) and E-III and E-IV for nine patients (28%). Endodermal sinus tumors and mixed germ cell tumors were the most commonly identified histological types. With a median follow-up of 7.8 years (95% confidence interval {CI}: 5.9-9.6), the event-free survival was 63.7%. The overall survival at a median follow-up of 9.1 years (95% CI: 7.5-10.7) was 76.1%. CONCLUSION: The BEP chemotherapy regimen offers promising results for treating testicular germ cell tumors in children and adolescents, characterized by its low toxicity and minimal late side effects. However, patients older than 11 years displayed more adverse histological indicators, advanced disease stages, and higher relapse and mortality rates.

Pediatric Blastic Plasmacytoid Dendritic Cell Neoplasm, Clinical Features and Immunophenotype: A Case Report.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare but aggressive malignancy with high mortality involving the skin and hematopoietic system. Clinical suspicion is difficult, and management of skin lesions is challenging due to their indolent course prior to dissemination. We describe a patient with isolated skin involvement who progressed to CD4+/CD56+ and CD123+ acute leukemia.

Mejoría en la supervivencia de los niños con leucemia mieloide aguda en el Instituto Nacional de Cancerología de Colombia / Improvement in the survival of children with acute myeloid leukemia at the Colombian National Cancer Institute

Resumen Objetivo: Describir las características demográficas y clínicas de los pacientes con leucemia mieloide aguda (LMA) no promielocítica, y evaluar la mortalidad y la supervivencia de los niños tratados con protocolo LMA-INC 2004 (modificado de BFM 93) en la clínica de oncología pediátrica del Instituto Nacional de Cancerología, desde su instauración y por un periodo de 10 años y medio de seguimiento (mayo de 2004 a diciembre de 2014). Pacientes y método: Estudio observacional descriptivo retrospectivo de una cohorte con análisis de supervivencia de los pacientes menores de 18 años de edad con diagnóstico LMA tratados con quimioterapia intensiva sin mantenimiento ni trasplante. El análisis de supervivencia se realizó usando el método de Kaplan Meir. Resultados: Se analizaron 41 pacientes con diagnóstico de LMA excepto LMA M3, tratados con protocolo LMA-INC 2004. Se logró remisión completa en el 75,6% de los pacientes. La tasa de recaída fue de 27,4% anual y la tasa de muertes de 20,3% durante el periodo. La supervivencia general acumulada a dos años fue de 60% y a cinco años del 53,5%, con promedio de seguimiento de 4,3 años (3,2 - 5,2 años), y la supervivencia libre de recaída a cinco años fue del 42% con un tiempo promedio de seguimiento de 3,5 años (3,3 - 4,6 años). Conclusión: Los resultados muestran mejoría del 30% en la supervivencia de los pacientes con LMA como resultado de un tratamiento más intenso, que incluye la administración de altas dosis de citarabina y mitoxantrone en la consolidación y la intensificación, y que implica mejoría en los cuidados de soporte.

Abstract Objective: To describe the demographic and clinical characteristics of patients with acute myeloid leukemia; and to evaluate the mortality and survival of children treated with the LMA-INC 2004 protocol (modified from BFM 93) in a pediatric oncology clinic of the Colombian National Cancer Institute (Instituto Nacional de Cancerología de Colombia) between May 2004 and December 2014. Patients and methods: Retrospective descriptive observational study of a cohort with survival analysis of patients aged under 18 years, with a diagnosis of acute myeloid leukemia, who were treated with intensive chemotherapy without maintenance or transplantation. The survival analysis was performed using the Kaplan-Meier method. Results: We analyzed 41 patients diagnosed with myeloid leukemia, except acute myeloid leukemia type M3, who were, treated with the LMA-INC 2004 protocol. Complete remission was achieved in 75.6% of patients. The annual relapse rate was 27.4%; and the death rate 20.3%. Cumulative overall survival at 2 and 5 years was 60% and 53.5% respectively, with an average follow-up of 4.3 years (3.2 - 5.2 years); and the 5-year relapse-free survival was 42%, with an average follow-up time of 3.5 years (3.3 - 4.6 years). Conclusion: The results showed a 30% improvement in the survival of patients with acute myeloid leukemia, attributed to a more intense treatment that included the administration of high doses of cytarabine and mitoxantrone in consolidation and intensification; which implies improvement in supportive care.

A strategy to improve treatment-related mortality and abandonment of therapy for childhood ALL in a developing country reveals the impact of treatment delays.

BACKGROUND: Treatment-related mortality and abandonment of therapy are major barriers to successful treatment of childhood acute lymphoblastic leukemia (ALL) in the developing world. PROCEDURE: A collaboration was undertaken between Instituto Nacional de Cancerologia (Bogota, Colombia), which serves a poor patient population in an upper-middle income country, and Dana-Farber/Boston Children's Cancer and Blood Disorders Center (Boston, USA). Several interventions aimed at reducing toxic deaths and abandonment were implemented, including a reduced-intensity treatment regimen and a psychosocial effort targeting abandonment. We performed a cohort study to assess impact. RESULTS: The Study Population comprised 99 children with ALL diagnosed between 2007 and 2010, and the Historic Cohort comprised 181 children treated prior to the study interventions (1995-2004). Significant improvements were achieved in the rate of deaths in complete remission (13% to 3%; P = 0.005), abandonment (32% to 9%; P < 0.001), and event-free survival with abandonment considered an event (47% to 65% at 2 years; P = 0.016). However, relapse rate did not improve. Medically unnecessary treatment delays were common, and landmark analysis revealed that initiating the PIII phase of therapy ≥4 weeks delayed predicted markedly inferior disease-free survival (P = 0.016). Conversely, patients who received therapy without excessive delays had outcomes approaching those achieved in high-income countries. CONCLUSIONS: Implementation of a twinning program was followed by reductions in abandonment and toxic deaths, but relapse rate did not improve. Inappropriate treatment delays were common and strongly predicted treatment failure. These findings highlight the importance of adherence to treatment schedule for effective therapy of ALL.

HSP-72 accelerated expression in mononuclear cells induced in vivo by acetyl salicylic acid can be reproduced in vitro when combined with H2O2.

BACKGROUND: Among NSAIDs acetyl salicylic acid remains as a valuable tool because of the variety of benefic prophylactic and therapeutic effects. Nevertheless, the molecular bases for these responses have not been complete understood. We explored the effect of acetyl salicylic acid on the heat shock response. RESULTS: Peripheral blood mononuclear cells from rats challenged with acetyl salicylic acid presented a faster kinetics of expression of HSP-72 messenger RNA and protein in response to in vitro heat shock. This effect reaches its maximum 2 h after treatment and disappeared after 5 h. On isolated peripheral blood mononuclear cells from untreated rats, incubation with acetyl salicylic acid was ineffective to produce priming, but this effect was mimicked when the cells were incubated with the combination of H2O2+ ASA. CONCLUSIONS: Administration of acetyl salicylic acid to rats alters HSP-72 expression mechanism in a way that it becomes more efficient in response to in vitro heat shock. The fact that in vitro acetyl salicylic acid alone did not induce this priming effect implies that in vivo other signals are required. Priming could be reproduces in vitro with the combination of acetyl salicylic acid+H2O2.

Non-steroidal anti-inflammatory drugs activate NADPH oxidase in adipocytes and raise the H2O2 pool to prevent cAMP-stimulated protein kinase a activation and inhibit lipolysis.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) -aspirin, naproxen, nimesulide, and piroxicam- lowered activation of type II cAMP-dependent protein kinase A (PKA-II) in isolated rat adipocytes, decreasing adrenaline- and dibutyryl cAMP (Bt2cAMP)-stimulated lipolysis. The molecular bases of insulin-like actions of NSAID were studied. RESULTS: Based on the reported inhibition of lipolysis by H2O2, catalase was successfully used to block NSAID inhibitory action on Bt2cAMP-stimulated lipolysis. NSAID, at (sub)micromolar range, induced an H2O2 burst in rat adipocyte plasma membranes and in whole adipocytes. NSAID-mediated rise of H2O2 was abrogated in adipocyte plasma membranes by: diphenyleneiodonium, an inhibitor of NADPH oxidase (NOX); the NOX4 antibody; and cytochrome c, trapping the NOX-formed superoxide. These three compounds prevented the inhibition of Bt2cAMP-stimulated lipolysis by NSAIDs. Inhibition of aquaporin-mediated H2O2 transport with AgNO3 in adipocytes allowed NOX activation but prevented the lipolysis inhibition promoted by NSAID: i.e., once synthesized, H2O2 must reach the lipolytic machinery. Since insulin inhibits adrenaline-stimulated lipolysis, the effect of aspirin on isoproterenol-stimulated lipolysis in rat adipocytes was studied. As expected, isoproterenol-mediated lipolysis was blunted by both insulin and aspirin. CONCLUSIONS: NSAIDs activate NOX4 in adipocytes to produce H2O2, which impairs cAMP-dependent PKA-II activation, thus preventing isoproterenol-activated lipolysis. H2O2 signaling in adipocytes is a novel and important cyclooxygenase-independent effect of NSAID.

Taurine in adipocytes prevents insulin-mediated H2O2 generation and activates Pka and lipolysis.

Among many actions assigned to taurine (Tau), the most abundant amino acid in numerous mammalian tissues, it prevents high-fat diet-induced obesity with increasing resting energy expenditure. To sustain this Tau action, the goal of the present study was to explore the acute effects of Tau on baseline and on adrenaline, insulin and their second messengers to modulate lipolysis in white adipose tissue (WAT) cells from rat epididymis. The Tau effects in this topic were compared with those recorded with Gly, Cys and Met. Tau on its own did not modify baseline lipolysis. Tau raised isoproterenol- and dibutyryl-cAMP (Bt2cAMP)-activated glycerol release. Gly diminished Bt2cAMP-activated glycerol release, and Cys and Met had no effect. Cyclic AMP-dependent activation of protein kinase A (PKA) in cell-free extracts decreased slightly by Gly and was unaltered by Cys, Met, and Tau. PKA catalytic activity in cell-free extracts was stimulated by Tau and unchanged by Cys, Gly and Met. Gly and Tau effects on PKA disappeared when these amino acids were withdrawn by gel filtration. Insulin-mediated NADPH-oxidase (NOX) raises H2O2 pool, which promotes PKA subunit oxidation, and precludes its cAMP activation; thus, lipolysis is diminished. Tau, but not Cys, Gly and Met, inhibited, by as much as 70%, insulin-mediated H2O2 pool increase. These data suggested that Tau raised lipolysis in adipocytes by two mechanisms: stimulating cAMP-dependent PKA catalytic activity and favoring PKA activation by cAMP as a consequence of lowering the H2O2 pool.

Consenso sobre diagnóstico y tratamiento de Leucemia Mieloide Crónica En Colombia / Consensus on diagnosis and treatment of chronic Myeloid Leukemia in Colombia

Objetivo: Unificar criterios para organizar el diagnóstico de la Leucemia Mieloide Crónica (LMC) y racionalizar el uso de nuevos medicamentos para su tratamiento. Métodos: se realizó una búsqueda estructurada de la literatura médica en la base de datos Medline en el Registro de Estudios Clínicos (CCTR) de la Biblioteca Cochrane y EMBSE, usando la plataforma OVID. Todoso los artículos fueron revisados por un comité central y los resultados fueron validados por hematólogos, oncólogos y otros especialistas en una reunión de consenso. Resultados: Se generaron 11 recomedaciones sobre diagnóstico (criterios definitorios), tratamiento (fase crónica, fase acelerada, crisis molecular, evolución clonal, etc), y seguimiento según fase y tratamiento base (remisión hematológica, respuesta citogenética, respuesta molecular, evolución clonal, etc). Conclusiones. los esquemas de tratamiento disponibles permiten mejorar la supervivencia y calidad de vida de los pacientes. Todo paiente con LMC requiere confirmación histológica y citogenética de su enfermedad. El inicio temprano del tratamiento con inhibidores de la tirosina-quinasa y el seguimiento estricto de las respuestas hematológica, citogenética y molecular permitirán adecuar o modificar la terapia de manera oportuna en pacientes resistentes primarios o secundarios.

Signaling the signal, cyclic AMP-dependent protein kinase inhibition by insulin-formed H2O2 and reactivation by thioredoxin.

Catecholamines in adipose tissue promote lipolysis via cAMP, whereas insulin stimulates lipogenesis. Here we show that H(2)O(2) generated by insulin in rat adipocytes impaired cAMP-mediated amplification cascade of lipolysis. These micromolar concentrations of H(2)O(2) added before cAMP suppressed cAMP activation of type IIbeta cyclic AMP-dependent protein kinase (PKA) holoenzyme, prevented hormone-sensitive lipase translocation from cytosol to storage droplets, and inhibited lipolysis. Similarly, H(2)O(2) impaired activation of type IIalpha PKA holoenzyme from bovine heart and from that reconstituted with regulatory IIalpha and catalytic alpha subunits. H(2)O(2) was ineffective (a) if these PKA holoenzymes were preincubated with cAMP, (b) if added to the catalytic alpha subunit, which is active independently of cAMP activation, and (c) if the catalytic alpha subunit was substituted by its C199A mutant in the reconstituted holoenzyme. H(2)O(2) inhibition of PKA activation remained after H(2)O(2) elimination by gel filtration but was reverted with dithiothreitol or with thioredoxin reductase plus thioredoxin. Electrophoresis of holoenzyme in SDS gels showed separation of catalytic and regulatory subunits after cAMP incubation but a single band after H(2)O(2) incubation. These data strongly suggest that H(2)O(2) promotes the formation of an intersubunit disulfide bond, impairing cAMP-dependent PKA activation. Phylogenetic analysis showed that Cys-97 is conserved only in type II regulatory subunits and not in type I regulatory subunits; hence, the redox regulation mechanism described is restricted to type II PKA-expressing tissues. In conclusion, phylogenetic analysis results, selective chemical behavior, and the privileged position in holoenzyme lead us to suggest that Cys-97 in regulatory IIalpha or IIbeta subunits is the residue forming the disulfide bond with Cys-199 in the PKA catalytic alpha subunit. A new molecular point for cross-talk among heterologous signal transduction pathways is demonstrated.

Ethanol-mediated oxidative changes in blood lipids and proteins are reversed by aspirin-like drugs.

BACKGROUND: Previous work from our laboratory revealed that administration of selected nonsteroidal anti-inflammatory drugs (NSAIDs)-aspirin, naproxen, nimesulide, and piroxicam-prevented some signs of oxidative stress produced in rat livers acutely intoxicated with ethanol. Our final aim was to pursue these advantageous effects of NSAIDs in humans in relation to opposing the oxidative action of ethanol. In preparation for these studies, we conducted a search for tissues that were more accessible than liver, such as plasma and blood cells. METHODS: Either ethanol (5 g/kg body weight) or an isocaloric amount of glucose from a 30% solution alone or combined with one of the NSAIDs was administered orogastrically to rats; animals were sacrificed 5 h later. RESULTS: Ethanol increased both protein carbonylation (PCO) and thiobarbituric acid reactive substances (TBARS) in isolated lymphocytes, increased proteolysis in isolated red blood cells (RBC), and decreased the pool of plasma amino acids. The NSAIDs employed reversed the ethanol-mediated rise in PCO in plasma, but with the exception of aspirin failed to prevent the ethanol-produced decrease in the amino-acid serum pool. Additionally, the increase in TBARS and PCO promoted by ethanol in lymphocytes was reverted with aspirin. In contrast, ethanol-activated proteolysis was not modified by aspirin. CONCLUSIONS: The pro-oxidant effects of ethanol and certain beneficial actions of NSAIDs, especially those of aspirin, preventing these pro-oxidant effects can be followed in blood constituents of rats. Hence, these oxidative markers could be regarded as potential clinical monitors for ethanol-mediated oxidative stress.

Relación entre el promedio de la enseñanza media superior y el rendimiento obtenido en el curso de bioquímica en medicina / Relation between average college marks and performance in biochemistry in medical school

Se relacionaron los promedios obtenidos en bioquímica por los alumnos de seis grupos correspondientes a seis generaciones (91-92 a 96-97) de la Facultad de Medicina de la UNAM con los promedios alcanzados por los mismos alumnos en la enseñanza media superior y provenientes principalmente de la Escuela Nacional Preparatoria y el Colegio de Ciencias y Humanidades. Se encontró una baja correlación entre las dos variables mencionadas. Los resultados de este estudio sugieren que en el desempeño de los alumnos durante el curso de bioquímica influyen otros factores además del promedio alcanzado en la enseñanza media superior que sería muy importante reconocer y analizar. Los alumnos provenientes de la Escuela Nacional Preparatoria tuvieron mejor rendimiento en el curso de bioquímica. Las diferencias observadas entre los dos sistemas de bachillerato permiten suponer que el de la Escuela Nacional Preparatoria es superior al del Colegio de Ciencias y Humanidades

Glutatión sanguíneo en gallinas ponedoras que consumieron diferentes pigmentos naturales y sudanes / Blood glutathione pool in layer hens fed different natural pigments and sudans

El objetivo de este trabajo fue medir la reserva de glutatión total (GT), glutatión reducido (GSH) y de glutatión oxidado (GSSG) sanguíneos, así como el color de la yema de huevo en gallinas tipo Leghorn (Dekalb Delta) de 59 semanas de edad. Los tratamientos por triplicado que se administraron durante 8 semanas fueron: Grupo I, alimento sin pigmento; grupo II, nueve ppm de xantofilas naturales amarillas (XNA) de la flor de cempasuchil; grupo III, nueve ppm de xna + 4 ppm de xantofilas naturales rojas (xnr) de los frutos de cápsicum; grupo IV, nueve ppm de xnr + 2 ppm de xantofilas sintéticas rojas (xsr); y grupo V, nueve ppm de xna + 9 ppm de sudanes rojos. Las aves fueron asignadas al azar a 15 grupos con 12 gallinas cada uno, alojadas en jaula. Semanalmente se midió el GT mediante espectrometría, y sólo en la semana 8 el GSH y el GSSG mediante cromatografía de líquidos de alta resolución (HPLC). La coloración de la yema de huevo se midió en el total de huevo producidos el día 35 de experimentación mediante un abanico colorimétrico y con un colorímetro de reflectancia. El color obtenido con el abanico Roche fue de: 1.0, 3.8, 10.4, 10.7 y 13.9 para los cinco grupos, respectivamente. No se observaron diferencias (P>0.05) en los parámetros productivos: consumo de alimento/ave/día, porcentaje de postura, conversión alimenticia y peso del huevo. Se observó diferencia significativa (P< 0.05) en el GT sanguíneo del grupo I (1.19 µmolas/ml), respecto del resto de los grupos (2.37, 1.95, 2.11 y 2.55 µmolas/ml, respectivamente) en la primera semana de experimentación. En la semana 8, el GSSG sanguíneo fue significativamente mayor en los grupos I y IV (10 y 12 nmolas/ml), comparado con los grupos II y III (7 y 9 nmolas/ml, respectivamente), y altamente significativo (P < 0.01) respecto del grupo V (5 nmolas/ml). En GSH no hubo diferencias entre tratamientos. Se concluye que el sudan se elimina a través de la yema de huevo y que no existió una relación clara entre los cambios en los niveles de glutatión y el consumo de algunos pigmentos en gallinas ponedoras

Glutatión sanguíneo en el paciente alcohólico con hepatopatía / Blood glutathione in the alcoholic patient with hepatopathy

Dada la gran importancia del glutatión como indicador de la reserva antioxidante tisular y en vista de la existencia de datos contradictorios en la literatura internacional, se decidió cuantificar la concentración del glutatión oxidado y del reducido en muestra de sangre de 18 individuos no bebedores y de 52 enfermos alcohólicos. El diagnóstico de los enfermos se hizo por medio de la clínica y estudios de laboratorio, lo que permitió agruparlos en tres grados crecientes de severidad de acuerdo al índice de Orrego. Se observó que existe un abatimiento de los niveles de glutatión total en sangre que es mayor conforme más severo es el daño hepático. El glutatión reducido en sangre, que es la fracción útil como antioxidante, muestra una disminución paralela al glutatión total; mientras que se observa un aumento en la fracción oxidada del glutatión sanguíneo, que guarda relación con la severidad del daño hepático. Se concluye que la determinación del glutatión total, así como sus fracciones reducida y oxidada, puede servir para conocer la reserva antioxidante en la sangre y probablemente en el organismo y con ello contribuye a evaluar las posibilidades de recuperación de los pacientes alcohólicos

Efecto de la furazolidona sobre el glutatión sanguíneo del pollo de engorda / Effec of furazolidone on chicks blood glutathione

El objetivo de este trabajo fue establecer si la furazolidona utiliza el sistema detoxificante de glutatión en el organismo, mediante la determinación de la cantidad (µmol/ml de sangre) de glutatión total (GT), glutatión oxidado (GSSG), y glutatión reducido (GSH) durante las 5 semanas de vida del pollo de engorda que no consumió aditivos (testigo), comparado con los niveles de GT, GSSG y GSH sanguíneo de las aves que consumieron furazolidona durante las 5 primeras semanas de vida. Hubo diferencia significativa entre el GT (µmol/ml de sangre) y el peso corporal de pollos del grupo testigo y el que consumió furazolidona (55 ppm en el alimento) (R²= -0.709; P< 0.05, y = 2.15 - 0.607x y R²=-0.820 P< 0.05, y = 2.17 -0.61x respectivamente) hubo diferencia significativa (P< 0.05) entre el peso de los pollos del grupo testigo y el de los que consumieron furazolidona (751.3 vs 884.35 g respectivamente)

Lipoperoxidación de las membranas de eritrocitos como un posible indicador del estrés oxidativo en el paciente alcohólico / Lipoperoxidation of the erythrocyte membranes as a possible oxidative stress indicator in the alcoholic patient

En este trabajo se estudia la lipoperoxidación de las membranas del eritrocito de pacientes alcohólicos como un idicador de estrés oxidativo ocasionado por un exceso de radicales libres generadas durante la exposición crónica al consumo exagerado de etanol. Las membranas eritrocíticas de los pacientes alcohólicos presentan un incremento de la lipoperoxidación es más notable en los sujetos cuya última ingesta etílica ha sucedido dentro de las 24 h que anteceden al estudio. Al correlacionar con el tiempo de alcoholismo se observa que el aumento de la lipoperoxidación ocurre desde los primeros 10 años de consumo de etanol y guarda relación con la cantidad de alcohol en gramos consumida por día. Se concluye que la determinación de la lipoperoxidación en membranas de eritrocito es un indicador del daño membranal por la ingesta aguda o crónica del etanol

Empleo de un antiinflamatorio en el control del daño hepático inducido con CCl4 / Use of anti-inflamatory drug on the control of liver cell damage induced by CCl4

El presente trabajo tiene como objetivo estudiar el posible efecto protector de un antiinflamatorio no esteroideo, piroxicam, en el daño hepático crónico inducido con CCl4 en un modelo experimental con ratas. Su evaluación se hace mediante parámetros bioquímicos y el estudio histológico de biopsias hepáticas. En las condiciones empleadas el uso del antiinflamatorio protege al hígado de los animales tratados con el hepatotóxico.