Cx43 Overexpression in Osteocytes Prevents Osteocyte Apoptosis and Preserves Cortical Bone Quality in Aging Mice

Young, skeletally mature mice lacking Cx43 in osteocytes exhibit increased osteocyte apoptosis and decreased bone strength, resembling the phenotype of old mice. Further, the expression of Cx43 in bone decreases with age, suggesting a contribution of reduced Cx43 levels to the age-related changes in the skeleton. We report herein that Cx43 overexpression in osteocytes achieved by using the DMP1-8kb promoter (Cx43OT mice) attenuates the skeletal cortical but not trabecular bone phenotype of aged, 14-month-old mice. The percentage of Cx43-expressing osteocytes was higher in Cx43OT mice, whereas the percentage of Cx43-positive osteoblasts remained similar to wild-type (WT) littermate control mice. The percentage of apoptotic osteocytes and osteoblasts was increased in aged WT mice compared with skeletally mature, 6-month-old WT mice, and the percentage of apoptotic osteocytes, but not osteoblasts, was decreased in age-matched Cx43OT mice. Aged WT mice exhibited decreased bone formation and increased bone resorption as quantified by histomorphometric analysis and circulating markers compared with skeletally mature mice. Further, aged WT mice exhibited the expected decrease in bone biomechanical structural and material properties compared with young mice. Cx43 overexpression prevented the increase in osteoclasts and decrease in bone formation on the endocortical surfaces and the changes in circulating markers in the aged mice. Moreover, the ability of bone to resist damage was preserved in aged Cx43OT mice both at the structural and material level. All together, these findings suggest that increased Cx43 expression in osteocytes ameliorates age-induced cortical bone changes by preserving osteocyte viability and maintaining bone formation, leading to improved bone strength. © 2018 American Society for Bone and Mineral Research

Marcadores de inflamación y perfil lipídico en pacientes obesos

La obesidad es una enfermedad metabólica asociada a insulinorresistencia (IR) y a un estado proinflamatorio, constituyendo un factor de riesgo de diabetes tipo 2 y enfermedad cardiovascular. En condiciones de obesidad, el tejido adiposo sufre una remodelación que favorece la síntesis de adipoquinas proinflamatorias y reactantes de fase aguda que promueven una inflamación crónica de bajo grado. El objetivo de este trabajo fue estudiar los niveles plasmáticos de Fibrinógeno (Fg), PCR ultrasensible (uPCR), TNF-α y mieloperoxidasa (MPO) en pacientes obesos y su correlación con IR e índices antropométricos. Se estudiaron 54 pacientes obesos (20M/34F), de 48±11años, que fueron comparados con 20 individuos sanos de sexo y edades semejantes. En ambos grupos se midió peso, talla, circunferencia de cintura (CC), se calculó el índice de masa corporal (IMC) y se determinó: glucemia y perfil lipídico (Wiener Lab), TNF-α (R&D Systems), MPO (Binding Site Ltd.), Fg (Diag.Stago), Insulina (ECLIA) y se calculó el HOMA. Los datos se analizaron con el programa SPSS 25 y se expresaron como la media±DS. Se consideró significativo un p<0,05. Los pacientes obesos, presentaron valores aumentados de: Fg (385±117 vs. 275±32 mg/dl, p=0,004); uPCR (7,4±5,6 vs. 1,4±1,6 m/dl, p=0,001); Insulina (23±16 vs. 7,2±2,4 uUI/ml, p=0,001), HOMA (5,2±3,9 vs. 2,1±0,3 p=0,001), Colesterol total (223±47 vs. 187±22 mg/dl, p=0,04) y LDL-C (150±45 vs.118±49 mg/dl, p=0,046). Sin embargo, los valores de TNF-α y MPO no mostraron diferencias significativas con los controles. El IMC se correlacionó positivamente con insulina, HOMA, Fg y uPCR, mientras que el CC lo hizo con insulina, HOMA y uPCR. Los resultados sugieren la presencia de un estado inflamatorio de bajo grado asociado a IR en pacientes obesos.Fil: Aleman, Mariano Nicolás. Universidad Nacional de Tucuman. Facultad de Bioquímica, Química y Farmacia. Instituto de Bioquímica Clinica Aplicada. Cátedra de Practica Profesional; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Luciardi, María Constanza. Universidad Nacional de Tucuman. Facultad de Bioquímica, Química y Farmacia. Instituto de Bioquímica Clinica Aplicada. Cátedra de Practica Profesional; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Díaz, E. L.. Universidad Nacional de Tucuman. Facultad de Bioquímica, Química y Farmacia. Instituto de Bioquímica Clinica Aplicada. Cátedra de Practica Profesional; ArgentinaFil: Mariani, A. C.. Universidad Nacional de Tucuman. Facultad de Bioquímica, Química y Farmacia. Instituto de Bioquímica Clinica Aplicada. Cátedra de Practica Profesional; ArgentinaFil: Herrera, Héctor Matías. Universidad Nacional de Tucuman. Facultad de Bioquímica, Química y Farmacia. Instituto de Bioquímica Clinica Aplicada. Cátedra de Practica Profesional; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Planta Piloto de Procesos Industriales Microbiológicos; ArgentinaFil: Albornoz, Estela Roxana. Universidad Nacional de Tucuman. Facultad de Bioquímica, Química y Farmacia. Instituto de Bioquímica Clinica Aplicada. Cátedra de Practica Profesional; ArgentinaFil: Valdez, M. E.. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia; ArgentinaFil: Abregu, Adela Victoria. Universidad Nacional de Tucuman. Facultad de Bioquímica, Química y Farmacia. Instituto de Bioquímica Clinica Aplicada. Cátedra de Practica Profesional; ArgentinaXXXVI Jornadas Científicas de la Asociación de Biología de TucumánArgentinaAsociación de Biología de Tucumá

Mitigating effects of vaccination on influenza outbreaks given constraints in stockpile size and daily administration capacity

<p>Abstract</p> <p>Background</p> <p>Influenza viruses are a major cause of morbidity and mortality worldwide. Vaccination remains a powerful tool for preventing or mitigating influenza outbreaks. Yet, vaccine supplies and daily administration capacities are limited, even in developed countries. Understanding how such constraints can alter the mitigating effects of vaccination is a crucial part of influenza preparedness plans. Mathematical models provide tools for government and medical officials to assess the impact of different vaccination strategies and plan accordingly. However, many existing models of vaccination employ several questionable assumptions, including a rate of vaccination <it>proportional </it>to the population at each point in time.</p> <p>Methods</p> <p>We present a SIR-like model that explicitly takes into account vaccine supply and the <it>number </it>of vaccines administered per day and places data-informed limits on these parameters. We refer to this as the <it>non-proportional </it>model of vaccination and compare it to the proportional scheme typically found in the literature.</p> <p>Results</p> <p>The proportional and non-proportional models behave similarly for a few different vaccination scenarios. However, there are parameter regimes involving the vaccination campaign duration and daily supply limit for which the non-proportional model predicts smaller epidemics that peak later, but may last longer, than those of the proportional model. We also use the non-proportional model to predict the mitigating effects of variably timed vaccination campaigns for different levels of vaccination coverage, using specific constraints on daily administration capacity.</p> <p>Conclusions</p> <p>The non-proportional model of vaccination is a theoretical improvement that provides more accurate predictions of the mitigating effects of vaccination on influenza outbreaks than the proportional model. In addition, parameters such as vaccine supply and daily administration limit can be easily adjusted to simulate conditions in developed and developing nations with a wide variety of financial and medical resources. Finally, the model can be used by government and medical officials to create customized pandemic preparedness plans based on the supply and administration constraints of specific communities.</p