ABSTRACT
Mesenchymal stem cell (MSC)-based therapy is being increasingly considered a powerful opportunity for several disorders based on MSC immunoregulatory properties. Nonetheless, MSC are versatile and plastic cells that require an efficient control of their features and functions for their optimal use in clinic. Recently, we have shown that PPARß/δ is pivotal for MSC immunoregulatory and therapeutic functions. However, the role of PPARß/δ on MSC metabolic activity and the relevance of PPARß/δ metabolic control on MSC immunosuppressive properties have never been addressed. Here, we demonstrate that PPARß/δ deficiency forces MSC metabolic adaptation increasing their glycolytic activity required for their immunoregulatory functions on Th1 and Th17 cells. Additionally, we show that the inhibition of the mitochondrial production of ATP in MSC expressing PPARß/δ, promotes their metabolic switch towards aerobic glycolysis to stably enhance their immunosuppressive capacities significantly. Altogether, these data demonstrate that PPARß/δ governs the immunoregulatory potential of MSC by dictating their metabolic reprogramming and pave the way for enhancing MSC immunoregulatory properties and counteracting their versatility.
Subject(s)
Mesenchymal Stem Cells/metabolism , PPAR-beta/metabolism , Receptors, Cytoplasmic and Nuclear/metabolism , Animals , Bone Marrow Cells/cytology , CD4-Positive T-Lymphocytes/cytology , Cell Proliferation , Gene Silencing , Glycolysis , Immunosuppression Therapy , Mice , Oligomycins/chemistry , Th1 Cells/cytology , Th17 Cells/cytologyABSTRACT
El uso de bloqueos de nervios para cirugías de cadera tiene beneficios demostrados. El bloqueo del grupo de nervios pericapsular es una técnica nueva que ha demostrado proveer una analgesia más satisfactoria para fracturas y artroplastias de cadera, en comparación con otros bloqueos más comúnmente usados para este tipo de cirugía. Este permite bloquear la inervación de la cápsula anterior a través del nervio obturador y las ramas articulares del femoral y obturador accesorio. Existen escasas publicaciones que describan el uso de catéteres perineurales para proveer analgesia continua utilizando esta técnica. Presentamos un caso de bloqueo continuo para analgesia preoperatoria, en un paciente que sufrió una fractura de columna y pared posterior de acetábulo, por aproximadamente 120 h. Al aumentar la velocidad de infusión se logró agregar analgesia para la región femoral distal. A diferencia de lo descrito previamente, el bloqueo se realizó utilizando un transductor de ultrasonido lineal
The use of peripheral nerve blockade for hip surgeries has proved to be beneficial. The PEricapsular Nerve Group block is a new technique described for hip fracture and hip arthroplasty that has shown to provide better analgesia compared to other peripheral blocks commonly performed for this type of surgery. This technique blocks the obturator nerve and the articular branches of the femoral nerve and the accessory obturator nerve. There are few reports describing continuous analgesia using catheters inserted in the pericapsular nerve group area. We describe a case of continuous nerve block for preoperative analgesia that lasted up to 120 hours in an adult patient with a fracture of the posterior column and wall of the acetabulum. We found that by increasing the infusion rate, analgesia reached the distal femoral area. Unlike the original technique, a high-frequency linear probe was used in this case
Subject(s)
Humans , Male , Middle Aged , Arthroplasty, Replacement, Hip/methods , Hip Fractures/surgery , Spinal Fractures/surgery , Acetabuloplasty/methods , Bupivacaine/administration & dosage , Anesthetics, Local/administration & dosage , Preoperative Care , Nerve Block/methods , Pain MeasurementABSTRACT
The use of peripheral nerve blockade for hip surgeries has proved to be beneficial. The PEricapsular Nerve Group block is a new technique described for hip fracture and hip arthroplasty that has shown to provide better analgesia compared to other peripheral blocks commonly performed for this type of surgery. This technique blocks the obturator nerve and the articular branches of the femoral nerve and the accessory obturator nerve. There are few reports describing continuous analgesia using catheters inserted in the pericapsular nerve group area. We describe a case of continuous nerve block for preoperative analgesia that lasted up to 120hours in an adult patient with a fracture of the posterior column and wall of the acetabulum. We found that by increasing the infusion rate, analgesia reached the distal femoral area. Unlike the original technique, a high-frequency linear probe was used in this case.
Subject(s)
Acetabulum/injuries , Analgesia/methods , Fractures, Bone/surgery , Hip Fractures/surgery , Nerve Block/methods , Anesthetics, Local/administration & dosage , Catheterization, Peripheral/methods , Femoral Nerve , Humans , Levobupivacaine/administration & dosage , Lidocaine/administration & dosage , Male , Middle Aged , Obturator Nerve , Psoas Muscles , Time Factors , Traction/adverse effectsABSTRACT
Studies conducted in monozygotic and dizygotic twins have established a strong genetic component in eating behavior. Rare mutations and common variants of the melanocortin 4 receptor (MC4R) gene have been linked to obesity and eating behavior scores. However, few studies have assessed common variants in MC4R gene with the rewarding value of food in children. The objective of the study was to evaluate the association between the MC4R rs17782313 polymorphism with homeostatic and non-homeostatic eating behavior patterns in Chileans children. This is a cross-sectional study in 258 Chilean children (44 % female, 8-14 years old) showing a wide variation in BMI. Anthropometric measurements (weight, height, Z-score of BMI and waist circumference) were performed by standard procedures. Eating behavior was assessed using the Eating in Absence of Hunger Questionnaire (EAHQ), the Child Eating Behavior Questionnaire (CEBQ), the Three-Factor Eating Questionnaire (TFEQ), and the Food Reinforcement Value Questionnaire (FRVQ). Genotype of the rs17782313 nearby MC4R was determined by a Taqman assay. Association of the rs17782313 C allele with eating behavior was assessed using non-parametric tests. We found that children carrying the CC genotype have higher scores of food responsiveness (p value = 0.02). In obese girls, carriers of the C allele showed lower scores of satiety responsiveness (p value = 0.02) and higher scores of uncontrolled eating (p value = 0.01). Obese boys carrying the C allele showed lower rewarding value of food in relation to non-carriers. The rs17782313 C allele is associated with eating behavior traits that may predispose obese children to increased energy intake and obesity (AU)
No disponible
Subject(s)
Humans , Male , Female , Child , Adolescent , Hyperphagia/genetics , Overweight/etiology , Pediatric Obesity/etiology , Polymorphism, Genetic , Genetic Predisposition to Disease , Receptor, Melanocortin, Type 4/genetics , Waist Circumference , Reward , Reinforcement, Psychology , Feeding Behavior , Alleles , Body Mass Index , Chile , Genetic Association StudiesABSTRACT
Studies conducted in monozygotic and dizygotic twins have established a strong genetic component in eating behavior. Rare mutations and common variants of the melanocortin 4 receptor (MC4R) gene have been linked to obesity and eating behavior scores. However, few studies have assessed common variants in MC4R gene with the rewarding value of food in children. The objective of the study was to evaluate the association between the MC4R rs17782313 polymorphism with homeostatic and non-homeostatic eating behavior patterns in Chileans children. This is a cross-sectional study in 258 Chilean children (44 % female, 8-14 years old) showing a wide variation in BMI. Anthropometric measurements (weight, height, Z-score of BMI and waist circumference) were performed by standard procedures. Eating behavior was assessed using the Eating in Absence of Hunger Questionnaire (EAHQ), the Child Eating Behavior Questionnaire (CEBQ), the Three-Factor Eating Questionnaire (TFEQ), and the Food Reinforcement Value Questionnaire (FRVQ). Genotype of the rs17782313 nearby MC4R was determined by a Taqman assay. Association of the rs17782313 C allele with eating behavior was assessed using non-parametric tests. We found that children carrying the CC genotype have higher scores of food responsiveness (p value = 0.02). In obese girls, carriers of the C allele showed lower scores of satiety responsiveness (p value = 0.02) and higher scores of uncontrolled eating (p value = 0.01). Obese boys carrying the C allele showed lower rewarding value of food in relation to non-carriers. The rs17782313 C allele is associated with eating behavior traits that may predispose obese children to increased energy intake and obesity.
