Mesoporous silica SBA-15 was prepared to evaluate its application as gentamicin drug delivery system. Two procedures were used to evaluate the delivery: calcined powder and disk conformed. The ...samples were charged with gentamicin sulphate and the experiments were carried out in vitro. No significant difference between powder and disk was observed in the tests. The release profiles exhibited a pronounced initial burst release effect of 60%, followed by a very slow release pattern. A new HPLC method was employed for calculated gentamicin amount in the delivery test. This method requires a small amount of sample, very advisable in these kinds of assays.
A synthesis strategy to tailor the acid sites location in ferrierite crystals has been developed. The zeolite catalysts were synthesised in fluoride medium using different combinations of organic ...structure directing agents (SDAs) in the absence of inorganic cations. Therefore, the negative charge associated to the incorporation of aluminium to the framework was compensated exclusively by the positive charge of the organic SDAs. In this way, Al sitting in the zeolite framework was driven by the specific location of the different SDA molecules within the zeolite void volume. Following this synthesis strategy, it has been found that the distribution of strongly acidic hydroxyl groups in the proton form of the zeolites obtained after removal of the organic templates was dependent on the combination of organic molecules used as SDAs. Moreover, the catalytic activity of the zeolites in
m-xylene and 1-butene isomerisation increased as the relative population of strong Brönsted acid groups in sterically constrained sites inside the ferrierite cavity decreased.
Al sitting in ferrierite crystals has been controlled by carrying out the zeolite synthesis with selected combinations of organic directing agents in fluoride medium. The catalytic activity for the isomerisation of linear butenes and
m-xylene increased as the relative population of strong Brönsted acid groups in sterically constrained sites inside the ferrierite cavity decreased.
Background
Near‐fatal asthma (NFA) is a heterogeneous clinical entity and several profiles of patients have been described according to different clinical, pathophysiological and histological ...features. However, there are no previous studies that identify in a unbiased way – using statistical methods such as clusters analysis – different phenotypes of NFA. Therefore, the aim of the present study was to identify and to characterize phenotypes of near fatal asthma using a cluster analysis.
Methods
Over a period of 2 years, 33 Spanish hospitals enrolled 179 asthmatics admitted for an episode of NFA. A cluster analysis using two‐steps algorithm was performed from data of 84 of these cases.
Results
The analysis defined three clusters of patients with NFA: cluster 1, the largest, including older patients with clinical and therapeutic criteria of severe asthma; cluster 2, with an high proportion of respiratory arrest (68%), impaired conciousness level (82%) and mechanical ventilation (93%); and cluster 3, which included younger patients, characterized by an insufficient anti‐inflammatory treatment and frequent sensitization to Alternaria alternata and soybean.
Conclusions
These results identify specific asthma phenotypes involved in NFA, confirming in part previous findings observed in studies with a clinical approach. The identification of patients with a specific NFA phenotype could suggest interventions to prevent future severe asthma exacerbations.
Diagnostic précoce de la maladie d’Alzheimer Saint-Aubert, L.; Puel, M.; Chollet, F. ...
Revue neurologique,
November 2012, Volume:
168, Issue:
11
Journal Article, Conference Proceeding
Peer reviewed
Le diagnostic de maladie d’Alzheimer (MA) ne peut être établi avec certitude que grâce à des preuves anatomopathologiques ou la découverte de mutations génétiques. Les critères diagnostiques actuels ...s’appuient sur des outils d’imagerie et biologiques innovants, afin de détecter les signes de la pathologie dès les stades les plus précoces, et ce avec les meilleures sensibilité et spécificité possibles.
Les progrès en neuro-imagerie ont permis de développer différents outils d’aide au diagnostique, comme l’évaluation de l’atrophie cérébrale en imagerie par résonance magnétique (IRM), et l’étude du métabolisme cérébral en tomographie par émission de positons (TEP). De plus, l’utilisation des marqueurs biologiques in vivo, combinée aux critères cliniques, permet de discriminer les patients à des stades de plus en plus précoces. C’est le cas de l’étude des concentrations en protéines tau et bêta-amyloïde dans le liquide céphalo-rachidien, et de la fixation de radioligands spécifiques de l’amyloïde.
Les outils d’aide au diagnostic sont de plus en plus nombreux et performants. Au vu de l’hétérogénéité clinique des patients, il apparaît essentiel d’associer différentes méthodes d’investigation pour pouvoir poser un diagnostic le plus précoce et le plus fiable possible.
Diagnosis of Alzheimer's disease (AD) remains difficult to establish, and can only be considered as certain thanks to anatomopathological evidence, or genetic mutations. Current diagnostic criteria rely on innovative imaging and biological tools, in order to detect pathological cues from very early stages, and with best sensibility and sensitivity.
Advances in neuro-imaging enabled the development of different tools to help establishing the diagnosis, such as cerebral atrophy assessment on magnetic resonance imaging (MRI), and cerebral metabolism study on positron emission tomography (PET). Besides, the increasing use of in vivo biological markers, combined to clinical criteria, enables to discriminate patients from healthy controls at even earlier stages. This includes studies on tau and beta-amyloid proteins concentrations in the cerebrosinal fluid, and amyloid-specific radioligands uptake. Familial forms of Alzheimer represent a great model for studying early or even pre-symptomatic AD, as genetic analyses constitute a diagnosis of certainty, even though they usually evolve earlier and faster.
Diagnostic tools are more and more numerous and performant. According to patients’ clinical heterogeneity, it appears essential to associate different method to investigate, in order to make a diagnosis as early and as reliable as possible.
Lexical-semantic impairment is one of the earliest symptoms of Alzheimer's disease (AD) and is usually examined by single word processing tasks. During speech production, pauses are often ...investigated as a hallmark of a patient's lexical-semantic decline. In the current study, we put forward the hypothesis that pauses reflect different processes according to the type of discourse. We believe that lexical and semantic impairment would predict a patient's pause frequency in a picture-based narrative (PBN) while anterograde memory would predict a patient's pause frequency in a memory-based narrative (MBN). To demonstrate this, we recruited 17 early AD patients and 17 matched controls. They underwent a full neuropsychological and language assessment and two narrative production assessments. We compared pause duration and frequency in the AD participants’ and healthy controls’ PBN and MBN. A multiple regression model was used in each narrative and in each group individually to assess the relationship between cognitive processes and pause frequency. Our results show that participants with AD produced more pauses in the PBN only. The frequency was predicted by semantic fluency performance with which it was positively correlated, contrary to what was expected. In the MBN, pause frequency in the AD participants was positively correlated with and predicted by their memory performance. We then examined the neuroanatomical correlates of pause frequency in the AD participants. Considering the PBN, pause frequency was also positively correlated with the grey matter density of the anterior temporal lobe. These findings suggest that patients use pauses as compensatory mechanisms in the earliest stages of AD. Pauses therefore may reflect the time required for the compensation and the realisation of a weak process depending on the narrative task and should be considered as a positive sign.
•Early AD patients use pauses differently according to the narrative type.•The frequency of pauses reflects different processes according to the narrative.•Patients use pauses as compensatory mechanisms in the earliest stages of AD.
The present work describes the incorporation of finely divided and well-dispersed Au species into SBA-15 mesoporous silica functionalized with mercaptopropyl groups, and the catalytic activity of the ...resulting Au-materials in the liquid phase oxidation of cyclohexene with molecular oxygen at atmospheric pressure. The gold entities have been prepared through a two-phase system described in the eighteenth century involving a solution of gold in a mixture of nitric acid and ammonium chloride (aqua regia) and rosemary oil. Gold nanoclusters, which present a disordered structure and sizes below 3nm, and even single gold atoms which may be anchored/stabilized through sulphur groups are found immobilized on the mesoporous support, but no gold nanoparticles (with well-defined structure and usually over ∼5nm) are detected. Such observations have been carried out by Cs-corrected STEM-HAADF where the visualization of bright spots is attributable to these individual entities. These materials are active in the oxidation of cyclohexene, but their relative activity is governed by the synthesis conditions. Partial aggregation of the gold entities into nanoparticles has been observed during the reaction, which are mainly responsible for the catalytic activity. The allylic oxidation of the cyclohexene ring over the double bond epoxidation is strongly favored, and at high conversion the two dominants products are 2-cyclohexen-1-one and 2-cyclohexen-1-ol.
Performing exome sequencing in 14 autosomal dominant early-onset Alzheimer disease (ADEOAD) index cases without mutation on known genes (amyloid precursor protein (APP), presenilin1 (PSEN1) and ...presenilin2 (PSEN2)), we found that in five patients, the SORL1 gene harbored unknown nonsense (n=1) or missense (n=4) mutations. These mutations were not retrieved in 1500 controls of same ethnic origin. In a replication sample, including 15 ADEOAD cases, 2 unknown non-synonymous mutations (1 missense, 1 nonsense) were retrieved, thus yielding to a total of 7/29 unknown mutations in the combined sample. Using in silico predictions, we conclude that these seven private mutations are likely to have a pathogenic effect. SORL1 encodes the Sortilin-related receptor LR11/SorLA, a protein involved in the control of amyloid beta peptide production. Our results suggest that besides the involvement of the APP and PSEN genes, further genetic heterogeneity, involving another gene of the same pathway is present in ADEOAD.
The influence of pore size of MCM-41 materials on drug delivery rate has been studied. In order to achieve this objective, small pore size MCM-41 materials have been synthesised from mixtures of two ...different alkyltrimethylammonium surfactants with chain length of 8 and 10 carbon atoms. The analgesic ibuprofen was introduced into the pore channels and its delivery to the media has been measured and compared with the delivery from bigger pore-sized MCM-41 obtained from surfactants of 12 and 16 atoms of carbon. This study has revealed that the delivery rate of ibuprofen in a simulating body fluid solution decreases as the pore size decreases in the range of 3.6–2.5 nm.
Abstract Aim This study evaluated the effect of the administration of melatonin, the chief secretory product of the pineal gland, on the body weight in male Wistar rats. Main methods The animals were ...housed for 4 months in cages equipped to log horizontal activity within a thermostatically-controlled chamber, under a 12 h/12 h light/dark photoperiod (lights on at 08:00 h). After acclimatization, the animals were divided into two groups: (1) control animals, and (2) melatonin-treated animals. Melatonin was administered in tap water (20 μg/ml), and fresh drinking fluid was changed twice weekly. Rats were fed a standard diet ad libitum. Key findings Food and water intake, body weight, the amplitude of the activity/rest rhythm (motor activity), and blood melatonin and glucose concentrations were measured. The administration of melatonin did not influence either food or water intake or glucose levels relative to those found in the control animals. However, melatonin administration reduced body weight gain and increased nocturnal locomotor activity. The peak concentration of melatonin was found at night coinciding with the increase in nocturnal activity. Significance The results show that exogenous melatonin reduces body weight gain without having marked effects on metabolism. This may be due in part to the increased nocturnal activity shown by the animals treated with the indoleamine.
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