Las metástasis óseas del cáncer

Las metástasis óseas representan un problema clínico devastador en las neoplasias más frecuentes, especialmente en el mieloma múltiple, mama, próstata, y pulmón. Las consecuencias incluyen dolores refractarios a analgésicos convencionales, osteolisis que conlleva en ocasiones compresión medular, fracturas patológicas, y trastornos metabólicos. Recientes avances en el diagnóstico mediante técnicas de imagen, así como diversas técnicas bioquímicas, han favorecido un certero diagnóstico y seguimiento. El aumento de la supervivencia se ha mejorado mediante una aproximación multimodal en los tratamientos con la combinación de la inhibición de la osteolisis, la cirugía ortopédica profiláctica y la radioterapia. Recientes progresos en la investigación básica han determinado la huella molecular de metástasis de un tumor capaz de predecir su proclividad metastásica. La investigación básica favorecerá un conocimiento de los mecanismos básicos y llevará a elucidar dianas moleculares que favorecerán el desarrollo de fármacos capaces de prevenir, amortiguar o bloquear el proceso metastático.Bone metastases represent a devastating clinical problem in the most frequent neoplasies, especially in multiple myeloma, tumours breast, prostate and lung. The consequences include pain which is refractory to conventional analgesics, osteolysis often leading to bone-marrow compression and pathological fractures, and metabolic disorders. Recent advances in diagnosis using imaging techniques as well as different biochemical techniques have helped accurate diagnosis and follow-up. The increase in survival has improved through a multimodal approach combining, inhibition of osteolysis, with prophylactic orthopaedic surgery and radiation therapy. Recent advances in basic research have determined the molecular metastatic that can predict its proclivity to metastasize. Basic research will improve understanding of the basic mechanisms and lead to the clarification of molecular targets that will help in the development of medicines capable of preventing, decreasing or blocking the metastatic process

Efectos divergentes de la inhibición de TGF-ß en metástasis óseas de cáncer de mama y pulmón

Fundamento: El objetivo de este estudio radica en la determinación de la validez del factor de crecimiento transformante β (TGF-β) como diana terapéutica en modelos de metástasis óseas derivadas de distintos tipos histopatológicos del cáncer de pulmón. Material y métodos: Ratones inmunodeprimidos de 4 semanas de edad inoculados con líneas de cáncer de pulmón y de mama fueron tratados con péptido inhibidor de la citoquina, péptido control o placebo. Se tomaron semanalmente medidas de bioluminiscencia y microrradiografías para determinar el efecto del tratamiento sobre la carga tumoral presente en los huesos largos y las lesiones metastásicas en los mismos. Resultados: El tratamiento con el péptido específico frente a TGF-β tiene un efecto protector en el hueso en los animales inoculados con la línea de cáncer de mama, a diferencia de lo ocurrido en los grupos de péptido control y placebo. Sin embargo, el tratamiento anti-TGF-β carece de efectos terapéuticos significativos sobre las metástasis óseas que se desarrollan en los animales inoculados con las líneas de cáncer de pulmón empleadas. Conclusiones: El carácter de TGF-β como posible diana terapéutica en metástasis en hueso es altamente dependiente del tipo y subtipos histopatológicos de tumor

Glutamatergic pallidothalamic projections and their implications in the pathophysiology of Parkinson's disease

GABAergic projections emitted from the entopeduncular nucleus (ENT) and the substantia nigra pars reticulata (SNr) innervate different thalamic nuclei and they are known to be hyperactive after dopaminergic depletion. Here we show that isoform 2 of the vesicular glutamate transporter (VGLUT2) is expressed by neurons in the ENT nucleus but not in the SNr. Indeed, dual in situ hybridization demonstrated that the ENT nucleus contains two different subpopulations of projection neurons, one single-expressing GAD65/67 mRNAs and another one that co-expresses either of the GAD isoforms together with VGLUT2 mRNA. Unilateral dopaminergic depletion induced marked changes in pallidothalamic-projecting neuron gene expression, resulting in increased expression of GAD65/67 mRNAs together with a clear down-regulation of VGLUT2 mRNA expression. Our results indicate that the increased thalamic inhibition typical of dopamine depletion might be explained by a synergistic effect of increased GABA outflow coupled to decreased glutamate levels, both neurotransmitters coming from ENT neurons

Glutamatergic pallidothalamic projections and their implications in the pathophysiology of Parkinson's disease

GABAergic projections emitted from the entopeduncular nucleus (ENT) and the substantia nigra pars reticulata (SNr) innervate different thalamic nuclei and they are known to be hyperactive after dopaminergic depletion. Here we show that isoform 2 of the vesicular glutamate transporter (VGLUT2) is expressed by neurons in the ENT nucleus but not in the SNr. Indeed, dual in situ hybridization demonstrated that the ENT nucleus contains two different subpopulations of projection neurons, one single-expressing GAD65/67 mRNAs and another one that co-expresses either of the GAD isoforms together with VGLUT2 mRNA. Unilateral dopaminergic depletion induced marked changes in pallidothalamic-projecting neuron gene expression, resulting in increased expression of GAD65/67 mRNAs together with a clear down-regulation of VGLUT2 mRNA expression. Our results indicate that the increased thalamic inhibition typical of dopamine depletion might be explained by a synergistic effect of increased GABA outflow coupled to decreased glutamate levels, both neurotransmitters coming from ENT neurons

Las metástasis óseas del cáncer

Las metástasis óseas representan un problema clínico devastador en las neoplasias más frecuentes, especialmente en el mieloma múltiple, mama, próstata, y pulmón. Las consecuencias incluyen dolores refractarios a analgésicos convencionales, osteolisis que conlleva en ocasiones compresión medular, fracturas patológicas, y trastornos metabólicos. Recientes avances en el diagnóstico mediante técnicas de imagen, así como diversas técnicas bioquímicas, han favorecido un certero diagnóstico y seguimiento. El aumento de la supervivencia se ha mejorado mediante una aproximación multimodal en los tratamientos con la combinación de la inhibición de la osteolisis, la cirugía ortopédica profiláctica y la radioterapia. Recientes progresos en la investigación básica han determinado la huella molecular de metástasis de un tumor capaz de predecir su proclividad metastásica. La investigación básica favorecerá un conocimiento de los mecanismos básicos y llevará a elucidar dianas moleculares que favorecerán el desarrollo de fármacos capaces de prevenir, amortiguar o bloquear el proceso metastático.Bone metastases represent a devastating clinical problem in the most frequent neoplasies, especially in multiple myeloma, tumours breast, prostate and lung. The consequences include pain which is refractory to conventional analgesics, osteolysis often leading to bone-marrow compression and pathological fractures, and metabolic disorders. Recent advances in diagnosis using imaging techniques as well as different biochemical techniques have helped accurate diagnosis and follow-up. The increase in survival has improved through a multimodal approach combining, inhibition of osteolysis, with prophylactic orthopaedic surgery and radiation therapy. Recent advances in basic research have determined the molecular metastatic that can predict its proclivity to metastasize. Basic research will improve understanding of the basic mechanisms and lead to the clarification of molecular targets that will help in the development of medicines capable of preventing, decreasing or blocking the metastatic process

Can dietary magnesium sources and buffer change the ruminal microbiota composition and fermentation of lactating dairy cows?

Magnesium oxide (MgO) is one of the most used Mg supplements in livestock. However, to avoid relying upon only one Mg source, it is important to have alternative Mg sources. Therefore, the objective of this study was to evaluate the effects of the interaction of two Mg sources with buffer use on the ruminal microbiota composition, ruminal fermentation, and nutrient digestibility in lactating dairy cows. Twenty lactating Holstein cows were blocked by parity and days in milk into five blocks with four cows each, in a 2 × 2 factorial design. Within blocks, cows were assigned to one of four treatments: 1) MgO; 2) MgO + Na sesquicarbonate (MgO+); 3) calcium–magnesium hydroxide (CaMgOH); 4) CaMgOH + Na sesquicarbonate (CaMgOH+). For 60 d, cows were individually fed a corn silage-based diet, and treatments were top-dressed. Ruminal fluid was collected via an orogastric tube, for analyses of the microbiota composition, volatile fatty acids (VFA), lactate, and ammonia nitrogen (NH3–N). The microbiota composition was analyzed using V4/16S rRNA gene sequencing, and taxonomy was assigned using the Silva database. Statistical analysis was carried out following the procedures of block design analysis, where block and cow were considered random variables. Effects of Mg source, buffer, and the interaction between Mg Source × Buffer were analyzed through orthogonal contrasts. There was no interaction effect of the two factors evaluated. There was a greater concentration of NH3–N, lactate, and butyrate in the ruminal fluid of cows fed with CaMg(OH)2, regardless of the buffer use. The increase in these fermentation intermediates/ end-products can be explained by an increase in abundance of micro-organisms of the genus Prevotella, Lactobacillus, and Butyrivibrio, which are micro-organisms mainly responsible for proteolysis, lactate-production, and butyrate-production in the rumen, respectively. Also, dietary buffer use did not affect the ruminal fermentation metabolites and pH; however, an improvement of the apparent total tract digestibility of dry matter (DM), organic matter (OM), neutral fiber detergent (NDF), and acid fiber detergent (ADF) were found for animals fed with dietary buffer. In summary, there was no interaction effect of buffer use and Mg source, whereas buffer improved total tract apparent digestibility of DM and OM through an increase in NDF and ADF digestibility and CaMg(OH)2 increased ruminal concentration of butyrate and abundance of butyrate-producing bacteria.UCR::Vicerrectoría de Docencia::Ciencias Agroalimentarias::Facultad de Ciencias Agroalimentarias::Escuela de Zootecni