Effect of intracolonic benzalkonium chloride on trinitrobenzene sulphonic acid-induced colitis in the rat

BACKGROUND: We investigated the effects of benzalkonium chloride (BAC) on trinitrobenzene sulphonic acid (TNBS)-induced colitis in rats. METHODS: TNBS was administered intrarectally before and/or after BAC treatment. In the first study, the effects of treatment with BAC 6, 12 or 24 h after TNBS were examined. In the second study, animals were treated with BAC before, after or before and after TNBS, and were examined 7 days later. The severity of colitis was assessed by macroscopic and histological scoring of the colonic damage and by determination of colonic myeloperoxidase (MPO) activity. Macrophages and CD4+ and CD8+ T cells were examined by immunohistochemistry. RESULTS: When BAC was instilled into the colon 6, 12 or 24 h after TNBS, weight loss and macroscopic and histological features of the colon were similar to that of controls (TNBS alone). In contrast, MPO activity was significantly reduced in all three groups post-treated with BAC. In the groups examined 7 days after TNBS treatment, rats post-treated with BAC exhibited increased weight gain and significantly reduced macroscopic damage and MPO activity compared to the TNBS control group. Rats pre-treated with BAC exhibited less macroscopic damage of the colon than rats receiving only TNBS, but histological damage, MPO and weight gain were unchanged from TNBS controls. Immunohistochemistry revealed that BAC pre-treatment increased the numbers of macrophages and T cells in the colon. After TNBS treatment, macrophage accumulation was evident in the colon, but T cells were scarce. However, these cells were preserved or enhanced in the colonic mucosa in TNBS-treated rats that had been pre-treated with BAC. CONCLUSIONS: Treatment with BAC, particularly after induction of colitis, produces a significant reduction in the severity of tissue injury and inflammation through mechanisms that are not fully understood.     

Genetic basis of neurological tumours

Neurological tumours are common neoplasms of both adults and children. Recent studies have begun to delineate the genetic abnormalities that underlie such tumours, and have implicated two classes of genes, oncogenes and tumour suppressor genes. Most investigations have focused on those astrocytomas that affect the cerebral hemispheres of adults, since these are the most common and malignant brain tumours. The high-grade astrocytomas that affect adults, such as glioblastoma multiforme, often have amplification of the epidermal growth factor receptor (EGFR) oncogene and loss of a variety of chromosomal loci that probably harbour tumour suppressor genes. Of the various tumour suppressor gene loci, the p53 gene on chromosome 17p has been studied most closely and has been shown to be mutated in both low- and high-grade astrocytomas. These genetic alterations may provide a means for subdividing astrocytomas into diagnostic categories. For instance, p53 gene mutations occur more commonly in glioblastomas from young adults and women, while EGFR gene amplification is more common in glioblastomas from older adults and men. For the other primary CNS tumours, genetic studies remain in their infancy. The neurocutaneous syndromes, such as neurofibromatosis types 1 and 2, have provided unique insights into neurological oncogenesis. The NF1 gene on chromosomes 17q and its product, neurofibromin, may be important in the formation of neurofibrosarcomas, while the NF2 gene on chromosome 22q and its product, merlin, are probably involved in the formation of schwannomas and other nervous system tumours. The further characterization of these and other neurological tumour genes will undoubtedly illuminate many other areas in neurooncology.     

Incorporating statistical information into expert classification systems to reduce classification costs

Interactive expert systems seek relevant information from a user in order to answer a query or to solve a problem that the user has posed. A fundamental design issue for such a system is therefore itsinformation-seeking strategy, which determines the order in which it asks questions or performs experiments to gain the information that it needs to respond to the user. This paper examines the problem of optimal knowledge acquisition through questioning in contexts where it is expensive or time-consuming to obtain the answers to questions. An abstract model of an expert classification system — considered as a set of logical classification rules supplemented by some statistical knowledge about attribute frequencies — is developed and applied to analyze the complexity and to present constructive algorithms for doing probabilistic question-based classification. New heuristics are presented that generalize previous results for optimal identification keys and questionnaires. For an important class of discrete discriminant analysis problems, these heuristics find optimal or near-optimal questioning strategies in a small fraction of the time required by an exact solution algorithm.     

Algorithms and complexity concerning the preemptive scheduling of periodic,real-time tasks on one processor

We investigate the preemptive scheduling of periodic, real-time task systems on one processor. First, we show that when all parameters to the system are integers, we may assume without loss of generality that all preemptions occur at integer time values. We then assume, for the remainder of the paper, that all parameters are indeed integers. We then give, as our main lemma, both necessary and sufficient conditions for a task system to be feasible on one processor. Although these conditions cannot, in general, be tested efficiently (unless P=NP), they do allow us to give efficient algorithms for deciding feasibility on one processor for certain types of periodic task systems. For example, we give a pseudo-polynomial-time algorithm for synchronous systems whose densities are bounded by a fixed constant less than 1. This algorithm represents an exponential improvement over the previous best algorithm. We also give a polynomial-time algorithm for systems having a fixed number of distinct types of tasks. Furthermore, we are able to use our main lemma to show that the feasibility problem for task systems on one processor is co-NP-complete in the strong sence. In order to show this last result, we first show the Simultaneous Congruences Problem to be NP-complete in the strong sense. Both of these last two results answer questions that have been open for ten years. We conclude by showing that for incomplete task systems, that is, task systems in which the start times are not specified, the feasibility problem is ₂ ^p -complete.This work was supported in part by National Science Foundation Grant No. CCR-8711579. Some of these results were presented at the 15th Symposium on Mathematical Foundations of Computer Science, 1990.     

Transporting Deformations of Face Emotions in the Shape Spaces: A Comparison of Different Approaches

Studying the changes of shape is a common concern in many scientific fields. We address here two problems: (1) quantifying the deformation between two given shapes and (2) transporting this deformation to morph a third shape. These operations can be done with or without point correspondence, depending on the availability of a surface matching algorithm, and on the type of mathematical procedure adopted. In computer vision, the re-targeting of emotions mapped on faces is a common application. We contrast here four different methods used for transporting the deformation toward a target once it was estimated upon the matching of two shapes. These methods come from very different fields such as computational anatomy, computer vision and biology. We used the large diffeomorphic deformation metric mapping and thin plate spline, in order to estimate deformations in a deformational trajectory of a human face experiencing different emotions. Then we use naive transport (NT), linear shift (LS), direct transport (DT) and fanning scheme (FS) to transport the estimated deformations toward four alien faces constituted by 240 homologous points and identifying a triangulation structure of 416 triangles. We used both local and global criteria for evaluating the performance of the 4 methods, e.g., the maintenance of the original deformation. We found DT, LS and FS very effective in recovering the original deformation while NT fails under several aspects in transporting the shape change. As the best method may differ depending on the application, we recommend carefully testing different methods in order to choose the best one for any specific application.

     

The Multifunctional Sactipeptide Ruminococcin C1 Displays Potent Antibacterial Activity In Vivo as Well as Other Beneficial Properties for Human Health

The world is on the verge of a major antibiotic crisis as the emergence of resistant bacteria is increasing, and very few novel molecules have been discovered since the 1960s. In this context, scientists have been exploring alternatives to conventional antibiotics, such as ribosomally synthesized and post-translationally modified peptides (RiPPs). Interestingly, the highly potent in vitro antibacterial activity and safety of ruminococcin C1, a recently discovered RiPP belonging to the sactipeptide subclass, has been demonstrated. The present results show that ruminococcin C1 is efficient at curing infection and at protecting challenged mice from Clostridium perfringens with a lower dose than the conventional antibiotic vancomycin. Moreover, antimicrobial peptide (AMP) is also effective against this pathogen in the complex microbial community of the gut environment, with a selective impact on a few bacterial genera, while maintaining a global homeostasis of the microbiome. In addition, ruminococcin C1 exhibits other biological activities that could be beneficial for human health, as well as other fields of applications. Overall, this study, by using an in vivo infection approach, confirms the antimicrobial clinical potential and highlights the multiple functional properties of ruminococcin C1, thus extending its therapeutic interest.     

Association of IgG1 Antibody Clearance with FcγRIIA Polymorphism and Platelet Count in Infliximab-Treated Patients

The FcγRIIA/CD32A is mainly expressed on platelets, myeloid and several endothelial cells. Its affinity is considered insufficient for allowing significant binding of monomeric IgG, while its H131R polymorphism (histidine > arginine at position 131) influences affinity for multimeric IgG2. Platelet FcγRIIA has been reported to contribute to IgG-containing immune-complexe clearance. Given our finding that platelet FcγRIIA actually binds monomeric IgG, we investigated the role of platelets and FcγRIIA in IgG antibody elimination. We used pharmacokinetics analysis of infliximab (IgG1) in individuals with controlled Crohn’s disease. The influence of platelet count and FcγRIIA polymorphism was quantified by multivariate linear modelling. The infliximab half-life increased with R allele number (13.2, 14.4 and 15.6 days for HH, HR and RR patients, respectively). It decreased with increasing platelet count in R carriers: from ≈20 days (RR) and ≈17 days (HR) at 150 × 10⁹/L, respectively, to ≈13 days (both HR and RR) at 350 × 10⁹/L. Moreover, a flow cytometry assay showed that infliximab and monomeric IgG1 bound efficiently to platelet FcγRIIA H and R allotypes, whereas panitumumab and IgG2 bound poorly to the latter. We propose that infliximab (and presumably any IgG1 antibody) elimination is partly due to an unappreciated mechanism dependent on binding to platelet FcγRIIA, which is probably tuned by its affinity for IgG2.     

Biowaste-derived hydroxyapatite reinforced with polyvinyl pyrrolidone/aloevera composite for biomedical applications

The present investigation focuses on the synthesis of crabshell-derived hydroxyapatite (CS-HAP)/ water-soluble synthetic polymer—polyvinylpyrrolidone(PVP)/aloevera(AV)—a natural biopolymer, as a composite for enhanced mechanical, antibacterial and biocompatible properties. The reinforcement of polymer has a significant function in increasing the mechanical property of the composite, whereas the incorporation of AV improves the antibacterial and biocompatibility. Phase composition, morphology, mechanical property, and hydrophilicity of CS-HAP/PVP/AV biocomposite with different concentrations of PVP and AV were examined by Fourier transform infrared spectroscopy (FTIR), X-Ray diffraction (XRD), scanning electron microscopy with energy dispersive X-ray (SEM-EDX), Vickers microhardness tests, contact angle, respectively. Furthermore, the antibacterial efficiency of the composite is assessed using Escherichia coli (E coli) and Staphylococcus aureus (S aureus). The biocompatibility of HOS MG 63 cells on the CS-HAP/PVP/AV composite is evaluated by MTT assay test. The obtained results evidence that the as-synthesized composite have appropriate mechanical, antibacterial and biocompatible properties. Overall, the combination of mechanical property of PVP, antibacterial and biocompatible property of AV in CS-HAP/PVP/AV, makes the composite a potential therapeutic material for various biomedical applications.     

Paf-acether in human skin

Paf is a phospholipid mediator present in human skin which induces inflammatory events such as neutrophil infiltration and increased vascular permeability. Recent data suggest that cutaneous cells, such as fibroblasts and keratinocytes, produce paf and that paf is released during allergic cutaneous reactions. It is tempting to speculate that paf may contribute to the development of various skin disorders with acute and chronic skin inflammation. Paf antagonists may help in bringing answers to this hypothesis and may offer new prospects for the treatment of cutaneous inflammatory diseases. Based on a paper presented at the Third International Conference on Platelet-Activating Factor and Structurally Related Alkyl Ether Lipids, Tokyo, Japan, May 1989.