Effect of ascorbic acid and epidermal growth factor in a rat tibia defect.

PURPOSE: Bone repair aims to restore the anatomical, biomechanical, and functional integrity of the affected structure. Here we study the effects of ascorbic acid (AA) and epidermal growth factor (EGF) applied in a single dose and in combination on the repair of a noncritical bone defect model. METHODS: Twenty-four rats were divided into four groups: an intact G-1 control group, and three groups that underwent a noncritical bone defect in the right tibia: G-2 treated with AA, G-3 treated with EGF, and G-4 treated with AA in combination with EGF. After 21 days of treatment, rats were sacrificed, the tibias were dissected and a destructive biomechanical analysis of three-point flexion test was performed in a universal testing machine; the values of stiffness, resistance, maximum energy, and energy at maximum load were statistically compared. RESULTS: G-3 and G-4 recovered the biomechanical properties of strength and stiffness of an intact tibia 3 weeks after their application. Not so the energy and energy at maximum load. For G-2, only the stiffness of an intact tibia was recovered. CONCLUSIONS: EGF and AA-EGF applied to a noncritical bone defect in the rat tibia favors the recovery of bone resistance and stiffness.

Effect of ascorbic acid and epidermal growth factor in a rat tibia defect

Purpose: Bone repair aims to restore the anatomical, biomechanical, and functional integrity of the affected structure. Here we study the effects of ascorbic acid (AA) and epidermal growth factor (EGF) applied in a single dose and in combination on the repair of a noncritical bone defect model. Methods: Twenty-four rats were divided into four groups: an intact G-1 control group, and three groups that underwent a noncritical bone defect in the right tibia: G-2 treated with AA, G-3 treated with EGF, and G-4 treated with AA in combination with EGF. After 21 days of treatment, rats were sacrificed, the tibias were dissected and a destructive biomechanical analysis of three-point flexion test was performed in a universal testing machine; the values of stiffness, resistance, maximum energy, and energy at maximum load were statistically compared. Results: G-3 and G-4 recovered the biomechanical properties of strength and stiffness of an intact tibia 3 weeks after their application. Not so the energy and energy at maximum load. For G-2, only the stiffness of an intact tibia was recovered. Conclusion: EGF and AA-EGF applied to a noncritical bone defect in the rat tibia favors the recovery of bone resistance and stiffness.

Tonic serotonergic input increases the burst firing mode and diminishes the firing rate of reticular thalamic nucleus neurons through 5-HT1A receptors activation in anesthetized rats.

The reticular thalamic nucleus (RTn) is a thin shell of GABAergic neurons that covers the dorsal thalamus that regulate the global activity of all thalamic nuclei. RTn controls the flow of information between thalamus and cerebral cortex since it receives glutamatergic information from collaterals of thalamo-cortical (TCs) and cortico-thalamic neurons. It also receives aminergic information from several brain stem nuclei, including serotonergic fibers originated in the dorsal raphe nucleus. RTn neurons express serotonergic receptors including the 5-HT1A subtype, however, the role of this receptor in the RTn electrical activity has been scarcely analyzed. In this work, we recorded in vivo the unitary spontaneous electrical activity of RTn neurons in anesthetized rats; our study aimed to obtain information about the effects of 5-HT1A receptors in RTn neurons. Local application of fluoxetine (a serotonin reuptake inhibitor) increases burst firing index accompanied by a decrease in the basal spiking rate. Local application of different doses of serotonin and 8-OH-DPAT (a specific 5-HT1A receptor agonist) causes a similar response to fluoxetine effects. Local 5-HT1A receptors blockade produces opposite effects and suppresses the effect by 8-OH-DPAT. Our findings indicate the presence of a serotonergic tonic discharge in the RTn that increases the burst firing index and simultaneously decreases the basal spiking frequency through 5-HT1A receptors activation.

Patterns of Active Commuting to School in Spanish Preschool Children and Its Associations with Socio-Economic Factors: The PREFIT Project.

The aims of this study were to describe patterns of active commuting to school (ACS) of preschool children, and to analyse the relationship between ACS and family socio-economic factors. A total of 2636 families of preschoolers (3-to-5 years old) were asked to complete a questionnaire at home about the mode of commuting to school of their children and marital status, educational level, and profession of both father and mother. Chi-square analyses were applied to compare ACS between school grades and gender of the children. To analyse the association of ACS with socio-economic factors, logistic regression analyses were performed. Almost 50% of participants reported ACS of their offspring, with a higher rate in 3rd preprimary grade (5 years old) than in 1st and 2nd preprimary grades (3- and 4-years old. All, p < 0.05). Those preschool children who had parents with lower educational level and no managerial work had higher odds to ACS than those who had parents with higher educational level and managerial work (all, p ≤ 0.001). Around half of the Spanish preschool children included in this study commuted actively to school and families with lower educational levels or worse employment situation were related to active commuting to school.

Fitness, waist circumference and their association with future blood pressure in youth: The UP&DOWN Longitudinal Study.

OBJECTIVES: The aim was to determine the independent associations of muscular fitness (MF), cardiorespiratory fitness (CRF) and waist circumference (WC) with blood pressure (BP) levels over 2 years in children and adolescents. METHODS: 1089 children (517 females) and 787 adolescents (378 females) with complete data on fitness, WC and BP (systolic [SBP] and diastolic [DBP]) were included. Upper MF was assessed through the handgrip strength test, and lower MF using the standing long jump test. The 20-m shuttle run test was used to assess CRF. WC was obtained following standardized methods. Different regression models were fitted by introducing fitness and WC at baseline and their changes as exposures and BP at follow-up and their changes as outcomes. RESULTS: WC at baseline was positively and independently associated with each BP variable at follow-up in children and adolescents (ß=0.094-0.260; p≤0.05), and CRF was negatively associated with DBP in adolescents (ß=-0.096; p=0.034). WC changes were associated with BP variables 2 years later in children (ß=0.121-0.142; p<0.01). In adolescents, changes in upper MF (ß=-0.116; p=0.001) and WC (ß=0.080-0.098; p<0.05) were associated with SBP at follow-up. WC changes were independently associated with changes in each BP variable in children (ß=0.111-0.145; all p<0.05) and SBP changes in adolescents (ß=0.103 to 0.117; all p<0.01). CONCLUSIONS: WC, but neither MF nor CRF, is independently associated with BP and its changes over 2 years. The attainment or maintenance of optimal fatness levels in the pediatric population should be highly encouraged for the prevention of future hypertension.

A castor oil plant (Ricinus communis)-derived implant improves the biomechanical properties of noncritical bone defects.

PURPOSE: The biomechanical properties of the polyurethanes implant material derived from castor oil plant (Ricinus communis) were evaluated in a noncritical bone defect model in rat tibia. METHODS: After three weeks of the implant application, the tibias were tested by means of the biomechanical three-point flexion test and resistance, rigidity, energy at maximum load and maximum energy were evaluated. Nonparametric statistical analysis was performed. RESULTS: It was found that the group that received the implant behaved the same as the intact control group and also showed a significant increase in maximum load compared to the spontaneous repair group. CONCLUSIONS: Our results indicate that the tibias with the implant material in a noncritical bone defect recover normal biomechanical parameters in less time than spontaneously.

A castor oil plant (Ricinus communis)-derived implant improves the biomechanical properties of noncritical bone defects

ABSTRACT Purpose The biomechanical properties of the polyurethanes implant material derived from castor oil plant (Ricinus communis) were evaluated in a noncritical bone defect model in rat tibia. Methods After three weeks of the implant application, the tibias were tested by means of the biomechanical three-point flexion test and resistance, rigidity, energy at maximum load and maximum energy were evaluated. Nonparametric statistical analysis was performed. Results It was found that the group that received the implant behaved the same as the intact control group and also showed a significant increase in maximum load compared to the spontaneous repair group. Conclusions Our results indicate that the tibias with the implant material in a noncritical bone defect recover normal biomechanical parameters in less time than spontaneously.

Changes in and the mediating role of physical activity in relation to active school transport, fitness and adiposity among Spanish youth: the UP&DOWN longitudinal study.

BACKGROUND: Longitudinal changes in child and adolescent active school transport (AST), and the mediating role of different intensities of daily physical activity (PA) levels in relation to AST and physical fitness and adiposity indicators is unclear. This study aimed to: 1) describe longitudinal changes in AST, light PA (LPA), moderate- to vigorous-intensity PA (MVPA), physical fitness and adiposity indicators over three time-points; and 2) investigate the mediating role of LPA and MVPA levels on associations between AST and physical fitness and adiposity indicators over three time-points among children and adolescents. METHODS: This longitudinal study comprised 1646 Spanish children and adolescents (48.8% girls, mean age 12.5 years ±2.5) at baseline, recruited from schools in Cádiz and Madrid. Mode of commuting to school was self-reported at baseline (T0, 2011-12), 1-year (T1) and 2-year follow-up (T2). PA was assessed using accelerometers. Handgrip strength, standing long jump and cardiorespiratory fitness (CRF) assessed physical fitness. Height, weight, body mass index, waist circumference, and triceps and subscapular skinfold thickness were measured. Multilevel linear regression analyses assessed changes in AST, PA levels, physical fitness and adiposity indicators over three time-points (T0-T1-T2). Additionally, longitudinal path analysis (n = 453; mean age [years] 12.6 ± 2.4) was used to test the mediating effects of LPA and MVPA levels on the association between AST and physical fitness and adiposity indicators. RESULTS: Multilevel analyses observed decreases in LPA between T0-T1 (ß = - 11.27; p < 0.001) and T0-T2 (ß = - 16.27; p < 0.001) and decreases in MVPA between T0-T2 (ß = - 4.51; p = 0.011). Moreover, changes over time showed increases in handgrip between T0-T1 (ß = 0.78; p = 0.028) and T0-T2 (ß = 0.81; p = 0.046). Path analyses showed that AST was directly positively associated with MVPA at T1 (all, ß ≈ 0.33; p < 0.001). MVPA at T1 mediated associations between AST and CRF at T2 (ß = 0.20; p = 0.040), but not the other outcomes. LPA did not mediate any associations. CONCLUSIONS: Results from longitudinal path analysis suggest that participation in more AST may help attenuate declines in MVPA that typically occur with age and improve CRF. Therefore, we encourage health authorities to promote AST, as a way to increase MVPA levels and CRF among youth.

Diet quality and well-being in children and adolescents: the UP&DOWN longitudinal study.

The present study examined the association between high-quality diet (using the Mediterranean diet (MD) as an example) and well-being cross-sectionally and prospectively in Spanish children and adolescents. Participants included 533 children and 987 adolescents at baseline and 527 children and 798 adolescents at 2-year follow-up, included in the UP&DOWN study (follow-up in schoolchildren and adolescents with and without Down's syndrome). The present study excluded participants with Down's syndrome. Adherence to an MD was assessed using the KIDMED index. Well-being was measured using the Positive and Negative Affect Schedule and the KIDSCREEN-10 questionnaire. Associations between MD adherence and well-being were assessed using multi-level, mixed-effects linear regression. At baseline, MD adherence was positively related to health-related quality of life in secondary school girls and boys (ß=0·41, se 0·10, P<0·001; ß=0·46, se 0·10, P<0·001, respectively) and to positive affect in secondary school girls and boys (ß=0·16, se 0·05, P=0·006; ß=0·20, se 0·05, P<0·001, respectively) and in primary school boys (ß=0·20, se 0·08, P=0·019). At 2-year follow-up, MD adherence was negatively related to negative affect in secondary school adolescent girls and boys (ß=-0·15, se 0·07, P=0·047; ß=-0·16, se 0·06, P=0·019, respectively), and MD adherence was associated with higher positive affect scores in secondary school girls (ß=0·30, se 0·06, P<0·001) and in primary school boys (ß=0·20, se 0·09, P=0·023). However, MD adherence at baseline did not predict well-being indicators at 2-year follow-up. In conclusion, higher MD adherence was found to behave as a protective factor for positive well-being in cross-sectional analysis.

Independent and combined associations of physical fitness components with inflammatory biomarkers in children and adolescents.

BACKGROUND: We aimed to examine the independent and combined associations of cardiorespiratory fitness, muscular fitness, and motor ability with single and clustered inflammatory biomarkers in children and adolescents. METHODS: This study included 503 children and adolescents. Cardiorespiratory fitness, upper- and lower-muscular fitness, and motor ability were assessed using field-based tests. Fasting blood samples were obtained to determine the levels of a set of inflammatory biomarkers. Global physical fitness and clustered inflammatory biomarker scores were computed. Associations between physical fitness and inflammatory biomarkers were analyzed through linear regression. Differences in inflammatory biomarker levels between physical fitness tertiles were tested. RESULTS: Global physical fitness was inversely associated with single and clustered inflammatory biomarkers in children (p < 0.05); and with C-reactive protein, complement factor C4, leptin, and clustered inflammatory biomarkers in adolescents (p < 0.025). Cardiorespiratory fitness and upper-muscular fitness were negatively and independently associated with several single and clustered inflammatory biomarkers in children and adolescents (p < 0.05). Differences were found between the lowest and the highest tertiles of global physical fitness in clustered inflammatory biomarker levels (p < 0.010). CONCLUSION: Physical fitness was negatively associated with single and clustered inflammatory biomarkers, independently of body mass index. Increasing physical fitness levels in youth might contribute to reduce the cardiovascular risk.

[Effect of BioOsteo® in combination with epidermal growth factor and ascorbic acid in a rat tibia defect]. / Efecto de BioOsteo® en combinación con el factor de crecimiento epidérmico y el ácido ascórbico en un defecto de la tibia de la rata.

BACKGROUND: Treatment of bone defects derived from trauma or from removal of tumors or osteosynthesis materials can cause socioeconomic problems as a result of treatment length. OBJECTIVE: The purpose of this study was to determine the effect of the implant material BioOsteo® in combinations with epidermal growth factor (EGF) and ascorbic acid (AA) on the consolidation of a non-critical size bone defect. MATERIALS AND METHODS: A unicortical non-critical bone defect was practiced in the right tibia of Wistar rats and 3 weeks later, a biomechanical property analysis was performed through a three-point bending test. RESULTS: We found that a 1 time single-dose local application of AA + EGF + BioOsteo, directly over the non-critical bone defect microenvironment improves its repair. ANTECEDENTES:: El tratamiento de los defectos óseos originados por traumatismos o por retiro de materiales de osteosíntesis o de tumores puede ocasionar problemas socioeconómicos derivados del tiempo de tratamiento. OBJETIVO:: Determinar el efecto del material de implante BioOsteo en combinación con factor de crecimiento epidérmico (EGF) y ácido ascórbico (AA) sobre la consolidación de un defecto óseo de tamaño no crítico. MATERIAL Y MÉTODOS:: Se practicó un defecto óseo unicortical no critico en la tibia derecha de ratas Wistar y 3 semanas después se realizó el análisis de las propiedades biomecánicas por medio del ensayo de flexión en tres puntos. RESULTADOS:: Encontramos que la aplicación local de una dosis única de AA + EGF + BioOsteo directamente sobre el microambiente del defecto óseo no crítico favorece su reparación.

Neck circumference and clustered cardiovascular risk factors in children and adolescents: cross-sectional study.

OBJECTIVE: Early detection of cardiovascular disease (CVD) risk factors, such as obesity, is crucial to prevent adverse long-term effects on individuals' health. Therefore, the aims were: (1) to explore the robustness of neck circumference (NC) as a predictor of CVD and examine its association with numerous anthropometric and body composition indices and (2) to release sex and age-specific NC cut-off values to classify youths as overweight/obese. DESIGN: Cross-sectional study. SETTING: 23 primary schools and 17 secondary schools from Spain. PARTICIPANTS: 2198 students (1060 girls), grades 1-4 and 7-10. MEASURES: Pubertal development, anthropometric and body composition indices, systolic and diastolic blood pressure (SBP and DBP, respectively), cardiorespiratory fitness, blood sampling triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), glucose and inflammatory markers. Homoeostasis model assessment (HOMA-IR) and cluster of CVD risk factors were calculated. RESULTS: NC was negatively associated with maximum oxygen consumption (R2=0.231, P<0.001 for boys; R2=0.018, P<0.001 for girls) and adiponectin (R2=0.049, P<0.001 for boys; R2=0.036, P<0.001 for girls); and positively associated with SBP, DBP, TC/HDL-c, TG, HOMA, complement factors C-3 and C-4, leptin and clustered CVD risk factor in both sexes (R2 from 0.035 to 0.353, P<0.01 for boys; R2 from 0.024 to 0.215, P<0.001 for girls). Moreover, NC was positively associated with serum C reactive protein and LDL-c only in boys (R2 from 0.013 to 0.055, P<0.05). CONCLUSION: NC is a simple, low-cost and practical screening tool of excess of upper body obesity and CVD risk factors in children and adolescents. Paediatricians can easily use it as a screening tool for overweight/obesity in children and adolescents. For this purpose, sex and age-specific thresholds to classify children and adolescents as normal weight or overweight/obese are provided.

Objectively Measured Physical Activity During Physical Education and School Recess and Their Associations With Academic Performance in Youth: The UP&DOWN Study.

BACKGROUND: This study examined the associations of objectively measured physical activity in Physical Education and recess with academic performance in youth. METHODS: This cross-sectional study was conducted with 1,780 participants aged 6 to 18 years (863 girls). Physical activity was objectively measured by accelerometry and was also classified according to sex- and agespecific quartiles of physical activity intensities. Academic performance was assessed through school records. RESULTS: Physical activity in physical education (PE) and recess was not associated with academic performance (ß ranging from -0.038 to -0.003; all P > .05). Youth in the lowest quartile of physical activity in PE engaged in an average of 1.40 min of moderate-to-vigorous physical activity and those in the highest quartile engaged in 21.60 min (for recess: lowest quartile, 2.20 min; highest quartile, 11.15 min). There were no differences in academic performance between quartiles of physical activity in Physical Education and recess. CONCLUSIONS: Time spent at different physical activity intensities during PE and recess does not impair academic performance in youth.

Striatum and globus pallidus control the electrical activity of reticular thalamic nuclei.

Through GABAergic fibers, globus pallidus (GP) coordinates basal ganglia global function. Electrical activity of GP neurons depends on their membrane properties and afferent fibers, including GABAergic fibers from striatum. In pathological conditions, abnormal electrical activity of GP neurons is associated with motor deficits. There is a GABAergic pathway from the GP to the reticular thalamic nucleus (RTn) whose contribution to RTn neurons electrical activity has received little attention. This fact called our attention because the RTn controls the overall information flow of thalamic nuclei to cerebral cortex. Here, we study the spontaneous electrical activity of RTn neurons recorded in vivo in anesthetized rats and under pharmacological activation or inhibition of the GP. We found that activation of GP predominantly diminishes the spontaneous RTn neurons firing rate and its inhibition increases their firing rate; however, both activation and inhibition of GP did not modified the burst index (BI) or the coefficient of variation (CV) of RTn neurons. Moreover, stimulation of striatum predominantly diminishes the spiking rate of GP cells and increases the spiking rate in RTn neurons without modifying the BI or CV in reticular neurons. Our data suggest a GP tight control over RTn spiking activity.

Dopamine-dependent modulation of rat globus pallidus excitation by nicotine acetylcholine receptors.

The globus pallidus (GP) coordinates information processing in the basal ganglia nuclei. The contribution of nicotinic cholinergic receptors (nAChRs) to the spiking activity of GP neurons is largely unknown. Several studies have reported that the effect of nAChRs in other nuclei depends on dopaminergic input. Via in vivo single unit extracellular recordings and intranuclear drug infusions, we analyzed the effects of local activation and blockade of nAChRs in neurons of both sham and 6-hydroxydopamine (6-OHDA)-lesioned rats. In sham rats, the local application of nicotine and edrophonium (an acetylcholinesterase inhibitor) increases GP neurons spiking rate. Local application of mecamylamine, a neuronal nicotinic cholinergic antagonist, diminishes pallidal neurons spiking rate, an effect not produced by d-tubocurarine, a peripheral nicotinic cholinergic antagonist. Moreover, mecamylamine blocks the excitatory effect evoked by nicotine and edrophonium. In 6-OHDA-lesioned rats, local infusion of nicotine does not change pallidal neurons firing rate. Our results show that there is a tonic cholinergic input to the GP that increases their spiking rate through the activation of nAChRs and that this effect depends on functional dopaminergic pathways.

Perceived environment in relation to objective and self-reported physical activity in Spanish youth. The UP&DOWN study.

The aims of the present study were to assess the association of environmental perception with objective and self-reported physical activity (PA) and the relation between environmental perception and meeting PA recommendations on children and adolescents. A sample of 1520 youth (770 boys) aged 8-18 years (12.1 ± 2.5 years) from the UP&DOWN study were included in the data analyses. Environmental perception was assessed with the short adapted version of the ALPHA environmental questionnaire. PA was objectively (accelerometers) and self-reported measured (PA Questionnaire for Children, Patient-centered Assessment and Counseling for Exercise Questionnaire and Finnish PA Index). Linear regression models were used to assess the association of environmental perception with PA. Bivariate logistic regression models were used to assess differences between environmental perception and meeting PA recommendations. Environmental perception was positively associated with both objective and self-reported PA. Some differences were found in the association of environmental perception and PA between sex- and age-specific groups. Youth who perceived a more favourable environment were more likely to meet PA recommendations (at least 60 min · day(-1) of moderate to vigorous PA (MVPA)). Results suggest that environmental perceptions of children and adolescents may play an important role in achieving higher levels of PA.

Classification and characterisation of SRF produced from different flows of processed MSW in the Navarra region and its co-combustion performance with olive tree pruning residues.

The scope of this work is to study the co-combustion of a solid recovered fuel (SRF) produced from household wastes and packaging wastes recovered from selective collection (SC) in the autonomous community of Navarra, located in the northeast of Spain. The municipal solid waste (MSW) is subjected to a mechanical biological treatment (MBT) in order to stabilize the organic matter and recover the recyclable materials as it is done for packaging wastes. Afterwards, rejects from this treatment plant were preconditioned and compressed by a pelletizing process to produce a secondary fuel according to quality and classification criteria of EN 15359, producing the so-called SRF. A fuel characterisation was carried out according to CEN standards and the SRF was classified as follows: NCV 2; Cl 3; Hg 1. SRF pellets were cofired with residual biomass pellets from olive tree pruning (OTP) in a bubbling fluidised bed combustor, as an option of energy recovery. The mixture of fuels, with a mixing ratio close to 50% by weight, showed a significant calorific value of 18.25 MJ/kg at 8% of moisture content. In addition, elemental composition of the mixture based on nitrogen (N), sulphur (S) and chlorine (Cl) (1% N, 0.2% S and 0.4% Cl) was not far from some herbaceous biomasses. The co-combustion showed good results as an energy recovery technology because of the synergies of both fuels, improving notably the combustion conditions and reducing significantly CO concentration, regarding to the combustion of OTP, though other contaminants such as NOx and HCl increased. During eight hours of stable operation, the concentration of dioxins and furans was measured obtaining a value of 7.68 ng/Nm(3) (toxic equivalence: i-TEQ of 0.33 ng/Nm(3)). Proportions of SRF lower than 50% in the mixtures should be tested in order to cut down the emissions of these pollutants, or an abatement system for organochloride compounds may be required.

Evaluation of 13-valent pneumococcal conjugate vaccine and concomitant meningococcal group C conjugate vaccine in healthy infants and toddlers in Spain.

BACKGROUND: Given the concurrent administration of multiple vaccines during routine pediatric immunizations, efforts to elucidate the potential interference of any vaccine on the immune response to the concomitantly administered antigens are fundamental to prelicensure clinical research. METHODS: This phase 3 randomized controlled trial of 13-valent pneumococcal conjugate vaccine (PCV13) versus 7-valent PCV (PCV7) assessed immune responses of concomitantly administered meningococcal group C conjugated to diphtheria toxin cross-reactive material 197 (MnCCV-CRM197) in a 2-dose infant series and 15-month toddler dose. RESULTS: 619 subjects were randomized, 315 to PCV13 and 304 to PCV7. MnCCV-CRM197-induced immune responses were similar between the PCV13 and PCV7 groups, with >97% of the subjects achieving a ≥1:8 meningococcal serum bactericidal assay (SBA) titer after both dose 2 and the toddler dose. Geometric mean titers were lower in the PCV13 group 191.22 (167.72, 218.02) versus 266.19 (234.86, 301.71) following dose 2 and 432.28 (361.22, 517.31) versus 730.84 (642.05, 831.91) following the toddler dose. The geometric mean (GM) meningococcal SBA titer ratios (PCV13/PCV7) were 0.72 after dose 2 and 0.59 after the toddler dose. The criteria for MnCCV-CRM197 non-inferiority for GM titers were satisfied after dose 2. Percent responders was similar up to titers of 1:128. PCV13 elicited substantial antipneumococcal responses against all 13 serotypes, with ≥90% of the subjects achieving an antibody concentration ≥0.35µg/mL after dose 3 in the infant series. Safety and tolerability were similar between the vaccine groups. CONCLUSIONS: Immunogenicity results of MnCCV-CRM197 for PCV13 compared with PCV7 included lower GMTs, but the clinical significance of this is unknown as the proportion of infants achieving protective MenC antibody titers was comparable in the two groups. Percent responders were similar up to titers of 1:128. PCV13 has an acceptable safety profile in infants and toddlers, while providing expanded coverage against pneumococcal disease.

Striatal input- and rate-dependent effects of muscarinic receptors on pallidal firing.

The globus pallidus (GP) plays a key role in the overall basal ganglia (BG) activity. Despite evidence of cholinergic inputs to GP, their role in the spiking activity of GP neurons has not received attention. We examine the effect of local activation and blockade of muscarinic receptors (MRs) in the spontaneous firing of GP neurons both in normal and ipsilateral striatum-lesioned rats. We found that activation of MRs produces heterogeneous responses in both normal and ipsilateral striatum-lesioned rats: in normal rats the response evoked by MRs depends on the predrug basal firing rate; the inhibition evoked by MRs is higher in normal rats than in striatum-lesioned rats; the number of neurons that undergo inhibition is lower in striatum-lesioned rats than in normal rats. Our data suggest that modulation of MRs in the GP depends on the firing rate before their activation and on the integrity of the striato-pallidal pathway.

(+)-(S)-trujillon, (+)-(S)-4-(2,2-diphenyl-1,3,2-oxazabolidin-5-oxo)propionic acid, a novel glutamatergic analog, modifies the activity of globus pallidus neurons by selective NMDA receptor activation.

Decreased levels of glutamate and changes in several markers of glutamatergic function occur in movement disorders and chronic psychiatric illnesses. Ionotropic glutamate receptors have been implicated in neuronal cell death, and have, therefore, been related to the process of neurodegenerative diseases. Drugs that interact with the glutamatergic system are important tools for the development of better therapies. We examined the effect of a new glutamatergic analog, (+)-(S)-4-(2,2-diphenyl-1,3,2-oxazabolidin-5-oxo)propionic acid, (+)-(S)-Trujillon, on the spontaneous globus pallidus neuronal activity of the anesthetized rat. (+)-(S)-Trujillon excited most pallidal neurons in a dose-dependent manner. Furthermore, blockade of NMDA receptors (NMDARs) inhibited the (+)-(S)-Trujillon-induced excitation, whereas blockade of AMPA/kainate receptors did not. In addition, computational docking studies showed micromolar-range affinities of (+)-(S)-Trujillon for NR2A NMDARs. Our results indicate that (+)-(S)-Trujillon selectively activates NMDARs, an effect that could prove to be a useful tool in the analysis of motor, behavioral, and cognitive disorders, where NMDAR-mediated signaling is altered.