Gi/o-Protein Coupled Receptors in the Aging Brain.

Cells translate extracellular signals to regulate processes such as differentiation, metabolism and proliferation, via transmembranar receptors. G protein-coupled receptors (GPCRs) belong to the largest family of transmembrane receptors, with over 800 members in the human species. Given the variety of key physiological functions regulated by GPCRs, these are main targets of existing drugs. During normal aging, alterations in the expression and activity of GPCRs have been observed. The central nervous system (CNS) is particularly affected by these alterations, which results in decreased brain functions, impaired neuroregeneration, and increased vulnerability to neuropathologies, such as Alzheimer's and Parkinson diseases. GPCRs signal via heterotrimeric G proteins, such as Go, the most abundant heterotrimeric G protein in CNS. We here review age-induced effects of GPCR signaling via the Gi/o subfamily at the CNS. During the aging process, a reduction in protein density is observed for almost half of the Gi/o-coupled GPCRs, particularly in age-vulnerable regions such as the frontal cortex, hippocampus, substantia nigra and striatum. Gi/o levels also tend to decrease with aging, particularly in regions such as the frontal cortex. Alterations in the expression and activity of GPCRs and coupled G proteins result from altered proteostasis, peroxidation of membranar lipids and age-associated neuronal degeneration and death, and have impact on aging hallmarks and age-related neuropathologies. Further, due to oligomerization of GPCRs at the membrane and their cooperative signaling, down-regulation of a specific Gi/o-coupled GPCR may affect signaling and drug targeting of other types/subtypes of GPCRs with which it dimerizes. Gi/o-coupled GPCRs receptorsomes are thus the focus of more effective therapeutic drugs aiming to prevent or revert the decline in brain functions and increased risk of neuropathologies at advanced ages.

Comorbidity between idiopathic overactive bladder and chronic migraine.

Objective We tested whether overactive bladder (OAB) and chronic migraine (CM) could be comorbid. Patients and methods CM women, aged 40-69 years, answered a validated OAB questionnaire. Prevalence data were compared with those reported in our country in the general population (GP) using the same questionnaire. Results We interviewed 231 CM women. Eighty-four met OAB criteria. OAB prevalence in CM patients was significantly higher than that found in the GP (36.4% vs. 21.8% in the GP; p = 0.0001). There were 34 CM women aged 40-49 years (34.3% vs. 15.2%; p = 0.001), 35 aged 50-59 years (38.9% vs. 21.7%; p = 0.004) and 15 aged 60-69 years (35.7% vs. 24.5%; p = 0.15) meeting OAB criteria. Seventy-seven (33% vs. 9.9%; p = 0.002) needed more than eight micturitions/24 h, 61 (26.4% vs. 8.1%, p = 0.002) experienced nocturia and 43 (18.6% vs. 8.1%; p = 0.001) urinary incontinence. Conclusion In this exploratory study, at least in women, OAB and CM are comorbid, which suggests shared mechanisms.

Utilidad y rendimiento diagnóstico de la punción lumbar en el servicio de urgencias / Usefulness and diagnostic efficiency of the lumbar puncture in the emergency service

Introducción: la punción lumbar es un procedimiento diagnóstico y terapéutico necesario para muchas enfermedades del sistema nervioso. Con base en la literatura actual, su utilidad en el servicio de urgencias de neurología no ha sido totalmente explorada. Objetivos: describir la frecuencia de la punción lumbar en el departamento de urgencias, su utilidad en el diagnóstico de enfermedades del sistema nervioso, y las características demográficas y clínicas más relevantes de los pacientes a quienes se les realizó el procedimiento. Materiales y métodos: realizamos un estudio observacional, descriptivo, de corte transversal. Se registraron prospectivamente los datos de todos los pacientes atendidos en el servicio de urgencias de Neurología del Hospital Occidente de Kennedy en Bogotá-Colombia, a quienes se les indicó punción lumbar durante el periodo comprendido entre enero de 2012 a julio de 2013. Resultados: se valoraron 3,161 pacientes en urgencias de neurología, y se realizaron 630 punciones lumbares (19,9%). Las principales indicaciones para realizar el procedimiento fueron: cefalea con signos de alarma (40,6%) y sospecha de neuroinfección (27,5%). El 32,2% (IC 95%: 28,5-35,8) de las punciones lumbares tuvo un resultado anormal. La utilidad de la punción lumbar disminuyó en el grupo de pacientes mayores de 65 años (24,5% n=26). Cuando se practica la punción lumbar por sospecha clínica de neuroinfección, la utilidad del procedimiento puede llegar a ser hasta del 40,46% (IC 95%: 33,1- 48,1). El antecedente de VIH tiene una asociación significativa para tener una punción lumbar anormal (p <0.0001). La cefalea (70,9% n= 144) y la fiebre (26,1% n= 53) fueron los síntomas más frecuentes del grupo de pacientes con punción lumbar anormal. La fiebre, los signos meníngeos sutiles y la rigidez nucal, fueron las variables clínicas que presentaron una significancia estadística (p <0,05), y estuvieron asociadas al diagnóstico definitivo de neuroinfección. ...