Directly Compressible Acetaminophen Compositions Prepared by Fluidized-Bed Granulation

Polyvinylpyrrolidone (PVP) in aqueous solution was used as a binding agent in a fluidized-bed system to agglomerate acetaminophen powder into directly compressible granules. It was found that a minimal amount of 5% w/w PVP in a concentration of 7.5% w/v or less was needed to produce granules with an acceptable flow and the corresponding tablets having enough hardness without capping. There was a strong correlation between the time for 80% dissolved (T₈₀) and the logarithm of granule volume-surface mean diameter. A directly compressible acetaminophen composition to manufacture tablets having a T₈₀ value less than 30 min can be prepared simply by adding an appropriate amount of disintegrant (crospovidone, sodium starch glycolate, or pregelatinized starch) to the agglomerated granules.     

Inhibiting effects of serotonin and serotonin antagonists on the migration of mononuclear leucocytes

The effect of serotonin and the serotonin antagonists ketanserin, methiotepine and ICS-205-930 on the migration of leucocytes was studied by using the sealed capillary migration technique. The migration of mononuclear leucocytes was inhibited by serotonin at 10(-4) and 10(-6)-10(-10)mol/l. An inhibition of the mononuclear leucocyte migration was also caused by ICS-205-930 at 10(-4)mol/l, ketanserin at 10(-4) and 10(-8)-10(-10)mol/l and methiotepine at 10(-4) and 10(-6)-10(-8)mol/l. No inhibiting effects of serotonin or the serotonin antagonists were found on the migration of polymorphonuclear leucocytes. Thus, both serotonin and serotonin antagonists may inhibit mononuclear leucocyte migration.     

Adenosine Signaling in Mast Cells and Allergic Diseases

Adenosine is a nucleoside involved in the pathogenesis of allergic diseases. Its effects are mediated through its binding to G protein-coupled receptors: A1, A2a, A2b and A3. The receptors differ in the type of G protein they recruit, in the effect on adenylyl cyclase (AC) activity and the downstream signaling pathway triggered. Adenosine can produce both an enhancement and an inhibition of mast cell degranulation, indicating that adenosine effects on these receptors is controversial and remains to be clarified. Depending on the study model, A1, A2b, and A3 receptors have shown anti- or pro-inflammatory activity. However, most studies reported an anti-inflammatory activity of A2a receptor. The precise knowledge of the adenosine mechanism of action may allow to develop more efficient therapies for allergic diseases by using selective agonist and antagonist against specific receptor subtypes.     

Tau Exon 10 Inclusion by PrPC through Downregulating GSK3β Activity

Tau protein is largely responsible for tauopathies, including Alzheimer’s disease (AD), where it accumulates in the brain as insoluble aggregates. Tau mRNA is regulated by alternative splicing, and inclusion or exclusion of exon 10 gives rise to the 3R and 4R isoforms respectively, whose balance is physiologically regulated. In this sense, one of the several factors that regulate alternative splicing of tau is GSK3β, whose activity is inhibited by the cellular prion protein (PrP^C), which has different physiological functions in neuroprotection and neuronal differentiation. Moreover, a relationship between PrP^C and tau expression levels has been reported during AD evolution. For this reason, in this study we aimed to analyze the role of PrP^C and the implication of GSK3β in the regulation of tau exon 10 alternative splicing. We used AD human samples and mouse models of PrP^C ablation and tau overexpression. In addition, we used primary neuronal cultures to develop functional studies. Our results revealed a paralleled association between PrP^C expression and tau 4R isoforms in all models analyzed. In this sense, reduction or ablation of PrP^C levels induces an increase in tau 3R/4R balance. More relevantly, our data points to GSK3β activity downstream from PrP^C in this phenomenon. Our results indicate that PrP^C plays a role in tau exon 10 inclusion through the inhibitory capacity of GSK3β.     

Data reconciliation and optimal operation of a catalytic naphtha reformer

The naphtha reforming process converts low-octane gasoline blending components to high-octane components for use in high-performance gasoline fuels. The reformer also has an important function as the producer of hydrogen to the refinery hydrotreaters. A process model based on a unit model structure, is used for estimation of the process condition using data reconciliation. Measurements are classified as redundant or non-redundant and the model variables are classified as observable, barely observable or unobservable. The computed uncertainty of the measured and unmeasured variables shows that even if a variable is observable it may have a very large uncertainty and may thereby be practically unobservable. The process condition at 21 data points, sampled from two years of operation, was reconciled and used to optimize the process operation. There are large seasonal variations in the reformer product price and two operational cases are studied. In case 1, the product price is high and throughput is maximized with respect to process and product quality constraints. In case 2, the product price is low and the throughput is minimized with respect to a low constraint on the hydrogen production. Based on the characteristics of the optimal operation, a “self optimizing” control structure is suggested for each of the two operational cases.     

Analysis of the HLA class I associated peptide repertoire in a hepatocellular carcinoma cell line reveals tumor-specific peptides as putative targets for immunotherapy

HLA class I molecules present peptides on the cell surface to CD8(+) T cells. The repertoire of peptides that associate to class I molecules represents the cellular proteome. Therefore, cells expressing different proteomes could generate different class I-associated peptide repertoires. A large number of peptides have been sequenced from HLA class I alleles, mostly from lymphoid cells. On the other hand, T cell immunotherapy is a goal in the fight against cancer, but the identification of T cell epitopes is a laborious task. Proteomic techniques allow the definition of putative T cell epitopes by the identification of HLA natural ligands in tumor cells. In this study, we have compared the HLA class I-associated peptide repertoire from the hepatocellular carcinoma (HCC) cell line SK-Hep-1 with that previously described from lymphoid cells. The analysis of the peptide pool confirmed that, as expected, the peptides from SK-Hep-1 derive from proteins localized in the same compartments as in lymphoid cells. Within this pool, we have identified 12 HLA class I peptides derived from HCC-related proteins. This confirms that tumor cell lines could be a good source of tumor associated antigens to be used, together with MS, to define putative epitopes for cytotoxic T cells from cancer patients.     

Segmentation of multiple sclerosis lesions in brain MRI: A review of automated approaches

Automatic segmentation of multiple sclerosis (MS) lesions in brain MRI has been widely investigated in recent years with the goal of helping MS diagnosis and patient follow-up. However, the performance of most of the algorithms still falls far below expert expectations. In this paper, we review the main approaches to automated MS lesion segmentation. The main features of the segmentation algorithms are analysed and the most recent important techniques are classified into different strategies according to their main principle, pointing out their strengths and weaknesses and suggesting new research directions. A qualitative and quantitative comparison of the results of the approaches analysed is also presented. Finally, possible future approaches to MS lesion segmentation are discussed.     

Multiplex Real-time PCR for the Simultaneous Detection of Salmonella spp. and Listeria monocytogenes in Food Samples

In this study, we have developed a rapid method for the simultaneous detection of Listeria monocytogenes and Salmonella spp. in foods, combining culture enrichment and a multiplex real-time polymerase chain reaction (PCR). The assay used two pre-existing primer-probe sets, labelled with different reporter dyes to enable the direct distinction of the original contaminating agent. Amplification efficiency and inclusivity/exclusivity of the combined assay was successfully assessed. The overall process included the culture enrichment based on the ISO standard, consisting of 24 h incubation in appropriate media (Half Fraser Broth for Listeria and buffered peptone water (BPW) for Salmonella), followed by a single DNA extraction of mixed enrichment aliquots, and real-time PCR detection of the hly and bipA genes of L. monocytogenes and Salmonella spp., respectively. An internal amplification control, co-amplified during the PCR run, was included in the assay to verify the results. The tool was evaluated with a variety of artificially inoculated samples of fresh products and ready to eat and cooked dishes, allowing the identification of the target pathogens down to 5 CFU/25 g of food sample. Moreover, the analysis saved a considerable amount of time compared to the ISO standard, being performed in less than 2 working days. Specificity, sensitivity and accuracy were satisfactorily tested by comparison to the standard methods ISO 11290-2:1998 and ISO 6579:2002, suggesting that the tool has a great potential as a reliable alternative for food safety assurance providing rapid detection of both pathogens in food samples.     

Co‐composting an animal fatty‐proteinaceous waste with a solid lignocellulosic by‐product from the olive oil industry (‘alperujo’)

BACKGROUND: The production of biodegradable wastes and their disposal cause a major financial problem in many industrial activities. Co‐composting was thought to be a feasible alternative for disposing of a strongly alkaline waste from the pharmaceutical industry (AW), mainly consisting of animal fats and partially hydrolysed proteins in a stable emulsion. The AW was added gradually, during the early phase of the composting process, to a substrate made up of ‘alperujo’ (AL), the wet, lignocellulosic, solid by‐product of the olive oil industry, and fresh horse manure, which was added to improve the physical structure of the composting substrate. RESULTS: The addition of AW reduced organic matter degradation during composting, enriched the amount of organic compounds in the water‐ and alkali‐soluble fractions and increased mineral salt contents. Thus, significantly higher electrical conductivity, humification indices and contents of organic matter, P, K and Na were recorded in the end‐composts resulting from AW treatments. However, the application of one AW‐based compost led to soil N immobilisation, as revealed by an incubation experiment, which must be considered in order to avoid potential N starvation in the short term. CONCLUSION: According to these results, composting can be used as a disposal alternative for AW, leading to end‐products with potential uses as organic amendments or fertilisers for agricultural systems. In addition, these composts could be used to produce alternative liquid organic fertilisers, based on the extraction of their humic‐like fraction. Copyright © 2009 Society of Chemical Industry