Sertraline associated with gold nanoparticles reduce cellular toxicity and induce sex-specific responses in behavior and neuroinflammation biomarkers in a mouse model of anxiety.

This study aimed to evaluate the effects of sertraline associated with gold nanoparticles (AuNPs) in vitro cell viability and in vivo behavior and inflammatory biomarkers in a mouse model of anxiety. Sertraline associated with AuNPs were synthesized and characterized. For the in vitro study, NIH3T3 and HT-22 cells were treated with different doses of sertraline, AuNPs, and sertraline + AuNPs and their viability was evaluated using the MTT assay. For the in vivo study, pregnant Swiss mice were administered a single dose of lipopolysaccharide (LPS) on the ninth day of gestation. The female and male offspring were divided into five treatment groups on PND 60 and administered chronic treatment for 28 days. The animals were subjected to behavioral testing and were subsequently euthanized. Their brains were collected and analyzed for inflammatory biomarkers. Sertraline associated with AuNPs exhibited significant changes in surface characteristics and increased diameters. Different doses of sertraline + AuNPs showed higher cell viability in NIH3T3 and HT-22 cells compared with sertraline alone. The offspring of LPS-treated dams exhibited anxiety-like behavior and neuroinflammatory biomarker changes during adulthood, which were ameliorated via sertraline + AuNPs treatment. The treatment response was sex-dependent and brain region-specific. These results suggest that AuNPs, which demonstrate potential to bind to other molecules, low toxicity, and reduced inflammation, can be synergistically used with sertraline to improve drug efficacy and safety by decreasing neuroinflammation and sertraline toxicity.

Patient characteristics affect hip contact forces during gait.

OBJECTIVE: To examine hip contact force (HCF), calculated through multibody modelling, in a large total hip replacement (THR) cohort stratified by patient characteristics such as body mass index (BMI), age and function. METHOD: 132 THR patients undertook one motion capture session of gait analysis at a self-selected walking speed. HCFs were then calculated using the AnyBody Modelling System. Patients were stratified into three BMI groups, five age groups, and finally three functional groups determined by their self-selected gait speed. By means of statistical parametric mapping (SPM), statistical analyses of the 1-dimensional time series were performed to separately evaluate the influence of age, BMI and functionality on HCF. RESULTS: The mean predicted HCFs were comparable to HCFs measured with instrumented prostheses reported in the literature. The SPM analysis revealed a statistically significant positive linear correlation between BMI and HCF, indicating that obese patients are more likely to experience higher HCF during most of the stance phase, while a statistically significant negative correlation with age was found only during the late swing-phase. Patients with higher functional ability exhibited significantly increased peak HCF, while patients with lower functional ability demonstrated lower HCFs overall and a pathological flattening of the typical double hump force profile. CONCLUSION: HCFs experienced at the bearing surface are highly dependent on patient characteristics. BMI and functional ability were determined to have the biggest influence on contact forces. Current preclinical testing standards do not reflect this.

[Epidemiology and clinical characteristics of primary congenital glaucoma]. / Épidémiologie et caractéristiques cliniques du glaucome congénital primitif.

INTRODUCTION: Primary congenital glaucoma (PCG) is a rare and sight threatening condition. Few large epidemiological studies are available in the literature concerning this condition. The purpose of the study was to evaluate the epidemiological and clinical characteristics of children affected by PCG. PATIENTS AND METHOD: Children affected by PCG, from 1 day to 3 years old at the time of diagnosis were retrospectively included between 1999 and 2014. The analysis concerned the pregnancy, family history, initial referral, clinical presentation with description of the classic findings in this condition, mean age at first consultation, duration of follow-up and presence of a delay in treatment, defined as a delay of over one month from the appearance of clinical signs until diagnosis. Two groups were defined according to age at appearance of the clinical signs: "early" group prior to 2 months old and "late" group beyond 2 months up until 3 years old. RESULTS: One hundred and forty-one eyes of 71 children were included, with 49.3% girls (n=35 children) and 50.7% boys (n=36 children) for a male:female ratio of 1.02. The "early" group included 50 children i.e. 70.3% of the population; the "late" group 21 children or 29.7% of the population. A first-degree family history of congenital glaucoma existed in 28% of cases (n=19). The average age at first consultation was 13.1 months for the entire population, and the mean duration of follow-up was 56.6 months. Involvement was bilateral in 99.3% of cases (n=70 children) and the most frequent clinical sign was buphthalmos in 64.5% of eyes (n=91 eyes). Treatment was delayed in 35.3% of cases (n=25 children). DISCUSSION AND CONCLUSION: This study is of particular relevance because it was performed over a long period and on a large population, considering the rare prevalence of the pathology, and has found epidemiological and clinical data comparable with those available in the literature for similar populations.

Long-term follow-up of patients treated with glatiramer acetate: a multicentre, multinational extension of the European/Canadian double-blind, placebo-controlled, MRI-monitored trial.

Glatiramer acetate (GA) is effective in reducing clinical and magnetic resonance imaging (MRI) activity in relapsing-remitting multiple sclerosis (RRMS). Serial long-term MRI data are lacking for large cohorts of GA-treated patients. The European/Canadian GA study consisted of two consecutive phases, each lasting nine months. The first treatment phase was randomized, double-blind and placebo-controlled. The second was an open-label, active treatment phase with daily administration of 20 mg GA subcutaneously for all patients. For the long-term follow-up (LTFU), dual echo, pre- and postgadolinium T1-weighted brain MRI scans were obtained with the same acquisition scheme as for the original trial and a neurological assessment was performed. Lesion volumes, normalized brain volumes and percentage brain volume changes (PBVC) were measured. One hundred and forty-two (63.4%) of the 224 patients who completed the two phases of the European/Canadian study underwent the LTFU after a mean period of 5.8 years (range: 5.3-6.4); 73 were treated with GA from study initiation. MRI measures at LTFU did not significantly differ between patients originally assigned to placebo and those who were always treated with GA, but the proportion of patients who did not require walking aids at LTFU was lower in the latter group (P=0.034). PBVC between baseline and LTFU was significantly correlated with lesion load at study entry. An earlier initiation of GA treatment in patients with active RRMS might, at least partially, have a favourable impact on long-term disease evolution.

Efecto de distintos anticoagulantes sobre índices plaquetarios / Theeffect of different anticoagulants on platelets index

El efecto de anticoagulantes sobre el recuento de plaquetas (CP), Plaquetocrito (PCT), volumen plauqetario medio (VPM) y amplitud de la distribución plaquetaria (PDW) fue evaluado en sangre venosa de pacientes ambulatorios a distintos intervalos de tiempo luego de la extracción. El CP basal fue realizado en cámara a partir de sangre capilar. La mediadel CP basal y CP inicial (tiempo 0= con EDTA, heparina o citrato fueron similares, al igual que las medidas del PCT, VPM y PDW inicial con EDTA o heparina. Durante el período de evaluación, el CP y el PDW en muestras con EDTA se mantuvieron constantes, mientras que el PCT y el VPM evidenciaron un aumento. Con heparina hubo disminución del CP y PCT, aumento sostenido del VPM y PDW. Además se constataron agregados plaquetarios en los frotis, perfiles de histogramas y alrmas leucocitarias asociados con un incremento de leucocitos. Con citrato, el CP corregido y los índices plaquetarios se mantuvieron constantes. Estos resulatdos indican que: 1) el citrato sódico es más conveniente para evaluar índices plaquetarios, 2) Con EDTA, se debe estandarizar el tiempo de análisis de las muestras para obtener resultados comparables, especialmente al evaluar VPM y 3) la heparina produce marcadas modificaciones de los índices plaquetarios (AU)

Efecto de distintos anticoagulantes sobre índices plaquetarios / Theeffect of different anticoagulants on platelets index

El efecto de anticoagulantes sobre el recuento de plaquetas (CP), Plaquetocrito (PCT), volumen plauqetario medio (VPM) y amplitud de la distribución plaquetaria (PDW) fue evaluado en sangre venosa de pacientes ambulatorios a distintos intervalos de tiempo luego de la extracción. El CP basal fue realizado en cámara a partir de sangre capilar. La mediadel CP basal y CP inicial (tiempo 0= con EDTA, heparina o citrato fueron similares, al igual que las medidas del PCT, VPM y PDW inicial con EDTA o heparina. Durante el período de evaluación, el CP y el PDW en muestras con EDTA se mantuvieron constantes, mientras que el PCT y el VPM evidenciaron un aumento. Con heparina hubo disminución del CP y PCT, aumento sostenido del VPM y PDW. Además se constataron agregados plaquetarios en los frotis, perfiles de histogramas y alrmas leucocitarias asociados con un incremento de leucocitos. Con citrato, el CP corregido y los índices plaquetarios se mantuvieron constantes. Estos resulatdos indican que: 1) el citrato sódico es más conveniente para evaluar índices plaquetarios, 2) Con EDTA, se debe estandarizar el tiempo de análisis de las muestras para obtener resultados comparables, especialmente al evaluar VPM y 3) la heparina produce marcadas modificaciones de los índices plaquetarios

[Etiology and precipitating factors of cyclic vomiting]. / Eziologia e fattori precipitanti del vomito ciclico.

The aim of the study was to determine the nature, severity, precipitants and associated features of attacks and the incidence of potential aetiological factors of cyclic vomiting syndrome (CVS). Ten patients (6 boys and 4 girls aged 2-12 years) with CVS, defined as recurrent episodes of vomiting with symptom-free intervals occurring two or more times per year, with episodes having a similar pattern and for which no other cause could be found, ten patients (7 boys and 3 girls aged 7-14 years) with migraine, defined as recurrent headache with symptom-free intervals and at least three of the following symptoms or associated findings: abdominal pain, nausea or vomiting, throbbing headache, unilateral location, associated aura (visual, sensory, motor), relief after sleeping and ten controls (6 boys and 4 girls aged 4-13 years) were studied. The mean age at onset of symptoms in patients with CVS was 3.9 years and the mean number of attacks per year was 4, the average duration of episodes was 20.5 hours and the mean number of school missed days were 6 per year. The mean age at onset of symptoms in patients with migraine was 7.6 years and the mean number of attacks per year was 9.9, the average duration of episodes was 8 hours and the mean number of school missed days were 6.4 per year. A family history of migraine was significantly higher in both groups of patients, compared with controls (p = 0.009). A personal history of headache and/or migraine and associated sign or symptoms like recurrent abdominal pains, limb pain and kinetosis was significantly higher in both patients compared with controls (p < 0.001). CVS is a chronic, disabling condition and is a migraine variant, with attacks usually precipitated by stress and intercurrent infections.

Effects of serum from HIV-infected subjects on the functional activity of polymorphonuclear neutrophils.

The oxidative capacity of polymorphonuclears neutrophils (PMN) was assessed in 17 subjects with asymptomatic infection (AI), 16 patients with acquired immnunodeficiency syndrome (AIDS) and 12 healthy normal subjects using a quantitative Nitroblue Tetrazolium (NBT) reduction test. The effect of the serum of patients on the functional activity of normal and patients' PMN was also investigated. The NBT reduction non stimulated and stimulated with zymosan particles in presence of normal serum was similar to normal controls in both groups of patients. The serum from 11 out of the 17 AI subjects (65%) induced an increase while the serum from 8 out of the 16 AIDS patients (50%) induced a diminution in the stimulated NBT reduction in normal and patients' PMN. Those effects did no, appear to be related to complement C3 and circulating immune complexes levels. These results are indicating that PMN of HIV-seropositive patients do not present an intrinsic disfunction and that the impact of serum factor/s affects the normal functionalism of these cells depending on the infection stages.

Effect of serum from HIV-infected subjects on superoxide production by polymorphonuclear neutrophils.

Superoxide (O2.-) production by polymorphonuclear neutrophils (PMN) was assessed in 17 subjects with asymptomatic infection (AI), 16 patients with acquired immunodeficiency syndrome (AIDS), and 12 healthy normal subjects. The effect of patients' serum on the oxidative activity of normal and patients' PMN was also investigated. The O2.- production, nonstimulated and stimulated with zymosan particles in the presence of normal serum, was similar to that of normal controls in both groups of patients. The serum from 11 out of the 17 AI subjects (65%) induced an increase in the stimulated O2.- production in normal and patients' PMN, while the serum from 8 out of the 16 AIDS patients (50%) induced a diminution. These effects did not appear to be related to complement C3 and circulating immune complex levels, but suggest that PMN of HIV-seropositive patients do not present an intrinsic dysfunction and that the impact of serum factor(s) affects the normal oxidative activity of these cells depending on the stage of infection.

Cerebral complications of coronary by-pass surgery. A prospective study.

A prospective study was undertaken of cerebral complications in 91 patients undergoing coronary by-pass surgery. Patients showing clinically relevant neurological complications had longer pump-times but did not differ in pre-operative variables. Worsening of neurological state correlated with duration of pump-time but not with pre-operative variables. Duration of pump-time appears to be the main predictor of neurological complications after coronary by-pass surgery.

Neurofunctional assessment of early phases of Alzheimer's disease: a preliminary note on hemispheric EEG characteristics during cognitive tasks.

EEG characteristics, in terms of power distribution in 1-4, 4-6, 6-8, 8-10, 10-13, 13-18, 18-30 Hz frequency bands were evaluated in six putative non-medicated male Alzheimer patients. The latter were compared with six age and sex-matched normal controls during both resting conditions and tactile identification tasks specific for the left and right hemispheres. The result indicate a significant difference in the power of the 8-10 frequency band between the two groups and a significant hypovariability in the 6-8 and 8-10 bands during tactile tasks: Alzheimer patients showed reduced power and, also, where less reactive, no differences between the left and right hemispheres having appeared. These findings seem to confirm the specificity of EEG modifications in Alzheimer's disease, even in the very early phases of the pathological process. Possible implications are discussed in the light of some biochemical hypotheses.

Quality extinction test and lateralized EEG focality: preliminary observations in a group of epileptic patients.

73 primary epileptic patients, grouped according to their clinical picture and EEG focality, were evaluated by means of a test of tactile extinction (Quality Extinction Test) in order to assess the usefulness of this test in detecting lateralized cerebral malfunctioning in neurological functional diseases. The data indicate an increase of tactile extinction in epileptic patients and a good relationship between side of focality and side of extinction.

Lateralized cerebral impairment in schizophrenia. A critical review.

The authors review the more recent areas of research in the field of cerebral lateralized dysfunction in schizophrenia. The different approach consistently suggest a definite degree of abnormality in hemispheric functioning in schizophrenic patients: nevertheless, the heterogeneity of patients' populations, as well as some inherent characteristic of the disease (i.e. duration of the illness, length of hospitalization, duration of drug treatment and psychopathological symptoms) should be taken into the account in order to obtain a more accurate definition of the cerebral impairment in schizophrenia.