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The high structural anisotropy and colloidal stability of cellulose nanofibrils' enable the creation of self-standing fibrillar hydrogel networks at very low solid contents. Adding methacrylate moieties on the surface of TEMPO oxidized CNFs allows the formation of more robust covalently crosslinked networks by free radical polymerization of acrylic monomers, exploiting the mechanical properties of these networks more efficiently. This technique yields strong and elastic networks but with an undefined network structure. In this work, we use acrylate-capped telechelic polymers derived from the step-growth polymerization of PEG diacrylate and dithiothreitol to crosslink methacrylated TEMPO-oxidized cellulose nanofibrils (MATO CNF). This combination resulted in flexible and strong hydrogels, as observed through rheological studies, compression and tensile loading. The structure and mechanical properties of these hydrogel networks were found to depend on the dimensions of the CNFs and polymer crosslinkers. The structure of the networks and the role of individual components were evaluated with SAXS (Small-Angle X-ray Scattering) and photo-rheology. A thorough understanding of hybrid CNF/polymer networks and how to best exploit the capacity of these networks enable further advancement of cellulose-based materials for applications in packaging, soft robotics, and biomedical engineering., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The fundamental understanding concerning cellulose-cellulose interactions under wet and dry conditions remains unclear. This is especially true regarding the drying-induced association of cellulose, commonly described as an irreversible phenomenon called hornification. A fundamental understanding of the mechanisms behind hornification would contribute to new drying techniques for cellulose-based materials in the pulp and paper industry while at the same time enhancing material properties and facilitating the recyclability of cellulose-rich materials. In the present work, the irreversible joining of cellulose-rich surfaces has been studied by subjecting cellulose nanofibril (CNF) films to different heat treatments to establish a link between reswelling properties, structural characteristics as well as chemical and mechanical analyses. A heating time/temperature dependence was observed for the reswelling of the CNF films, which is related to the extent of hornification and is different for different chemical compositions of the fibrils. Further, the results indicate that hornification is related to a diffusion process and that the reswellability increases very slowly over long time, indicating that equilibrium is not reached. Hence, hornification is suggested to be a kinetically limited phenomenon governed by non-covalent reversible interactions and a time/temperature dependence on their forming and breaking., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Thorough characterization and fundamental understanding of cellulose fibers can help us develop new, sustainable material streams and advanced functional materials. As an emerging nanomaterial, cellulose nanofibrils (CNFs) have high specific surface area and good mechanical properties; however, handling and processing challenges have limited their widespread use. This work reports an in-depth characterization of self-fibrillating cellulose fibers (SFFs) and their use in smart, responsive filters capable of regulating flow and retaining nanoscale particles. By combining direct and indirect characterization methods with polyelectrolyte swelling theories, it was shown that introduction of charges and decreased supramolecular order in the fiber wall were responsible for the exceptional swelling and nanofibrillation of SFFs. Different microscopy techniques were used to visualize the swelling of SFFs before, during, and after nanofibrillation. Through filtration and pH adjustment, smart filters prepared via in situ nanofibrillation showed an ability to regulate the flow rate through the filter and a capacity of retaining 95% of 300 nm (diameter) silica nanoparticles. This exceptionally rapid and efficient approach for making smart filters directly addresses the challenges associated with dewatering of CNFs and bridges the gap between science and technology, making the widespread use of CNFs in high-performance materials a not-so-distant reality.

The biotechnological applications of cellulose nanocrystals (CNCs) continue to grow due to their sustainable nature, impressive mechanical, rheological, and emulsifying properties, upscaled production capacity, and compatibility with other materials, such as protein and polysaccharides. In this study, hydrogels from CNCs and pectin, a plant cell wall polysaccharide broadly used in food and pharma, were produced by calcium ion-mediated internal ionotropic gelation (IG). In the absence of pectin, a minimum of 4 wt% CNC was needed to produce self-supporting gels by internal IG, whereas the addition of pectin at 0.5 wt% enabled hydrogel formation at CNC contents as low as 0.5 wt%. Experimental data indicate that CNCs and pectin interact to give robust and self-supporting hydrogels at solid contents below 2.5 %. Potential applications of these gels could be as carriers for controlled release, scaffolds for cell growth, or wherever else distinct and porous network morphologies are required., (Copyright © 2020. Published by Elsevier Ltd.)

Objective: Both psoriatic arthritis (PsA) and rheumatoid arthritis (RA) have a significant impact on quality of life, but few reports have compared the two diseases. The current study assessed health-related quality of life (HRQoL) in PsA at diagnosis and after five years compared with early rheumatoid arthritis (RA) and a matched general population., Methods: Patients with early PsA and early RA included in two Swedish registries with HRQoL data measured by the Medical Outcomes Study Short Form 36 (SF-36) at baseline and at five years follow-up were included. Differences in SF-36 scores compared with the general population were calculated for each patient. Physical function, disease activity, the delay before diagnosis, pain, and general wellbeing were used as explanatory variables. Statistical tests included t-tests and univariate and multivariate linear regression., Results: PsA (n = 166) and RA (n = 133) patients of both sexes had significantly reduced HRQoL at disease onset. After five years, PsA patients still had impairments in several domains of SF-36, whereas RA patients had an almost normalized HRQoL. The time from symptom onset to diagnosis, disease activity, and disability independently contributed to the reduced improvement in PsA., Conclusion: Both early PsA and RA are characterized by severely reduced HRQoL. Despite more severe disease at inclusion, normalization of HRQoL is seen in patients with RA but not PsA. This may be due to delay in the diagnosis of PsA or more powerful interventions in RA. Earlier detection, lifestyle intervention, and more aggressive management strategies may be needed for PsA., Competing Interests: Declaration of Competing Interest In addition to academic research at Lund University, ET has been employee of Janssen Cilag since 2015. MG has received consultancy fees from AbbVie, Novartis and Pfizer (unrelated to the present work). There are no other conflict interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Bio-based nanocellulose has been shown to possess impressive mechanical properties and simplicity for chemical modifications. The chemical properties are largely influenced by the surface area and functionality of the nanoscale materials. However, finding the typical cross-sections of nanocellulose, such as cellulose nanofibers (CNFs), has been a long-standing puzzle, where subtle changes in extraction methods seem to yield different shapes and dimensions. Here, we extracted CNFs from wood with two different oxidation methods and variations in degree of oxidation and high-pressure homogenization. The cross-sections of CNFs were characterized by small-angle X-ray scattering and wide-angle X-ray diffraction in dispersed and freeze-dried states, respectively, where the results were analyzed by assuming that the cross-sectional distribution was quantized with an 18-chain elementary microfibril, the building block of the cell wall. We find that the results agree well with a pseudosquare unit having a size of about 2.4 nm regardless of sample, while the aggregate level strongly depends on the extraction conditions. Furthermore, we find that aggregates have a preferred cohesion of phase boundaries parallel to the (110)-plane of the cellulose fibril, leading to a ribbon shape on average.

Cellulose-based model materials in the form of fibrillar networks and macromolecular hydrogels were used to investigate the ion-induced swelling in relation to the elasticity and structure of the network. Both networks were charged by the introduction of carboxyl groups onto the cellulose surface, and the dimensions of the networks in aqueous solution were measured as a function of pH. The use of cellulose-model materials that contained either noncrystalline cellulose or cellulose I fibrils made it possible to model the effect of the ion-induced osmotic pressure of a delignified wood fiber wall. The noncrystalline hydrogels represented the noncrystalline domains of the fiber wall and the fibrillar network represented the supramolecular network of cellulose I fibrils of the fiber wall. The experimental results were compared to swelling potentials computed using the Donnan theory, and it was found that the ion-induced water uptake within the cellulose networks followed the theoretical predictions to a large extent. However, fibrillar networks were found to plastically deform upon swelling and deviated from the ideal Donnan theory for polyelectrolyte gel networks. Upon addition of salt to the aqueous phase surrounding the cellulose materials, both hydrogels and fibrillar networks deviated from the Donnan theory predictions, suggesting that structural differences between the networks impact their swelling.

Nanocomposites from native cellulose with low 2D nanoplatelet content are of interest as sustainable materials combining functional and structural performance. Cellulose nanofibril-graphene oxide (CNF-GO) nanocomposite films are prepared by a physical mixing-drying method, with focus on low GO content, the use of very large GO platelets (2-45μm) and nanostructural characterization using synchrotron x-ray source for WAXS and SAXS. These nanocomposites can be used as transparent coatings, strong films or membranes, as gas barriers or in laminated form. CNF nanofibrils with random in-plane orientation, form a continuous non-porous matrix with GO platelets oriented in-plane. GO reinforcement mechanisms in CNF are investigated, and relationships between nanostructure and suspension rheology, mechanical properties, optical transmittance and oxygen barrier properties are investigated as a function of GO content. A much higher modulus reinforcement efficency is observed than in previous polymer-GO studies. The absolute values for modulus and ultimate strength are as high as 17 GPa and 250 MPa at a GO content as small as 0.07 vol%. The remarkable reinforcement efficiency is due to improved organization of the CNF matrix; and this GO-induced mechanism is of general interest for nanostructural tailoring of CNF-2D nanoplatelet composites., Competing Interests: Conflicts of interest There are no conflicts to declare.

In this study, the effect of different alcohols and esters as a coagulation medium in the regeneration of cellulose dissolved in an aqueous LiOH-urea-based solvent was thoroughly investigated using various methods such as solid state NMR, X-ray diffraction, water contact angle, oxygen gas permeability, mechanical testing, and scanning electron microscopy. It was observed that several material properties of the regenerated cellulose films follow trends that correlate to the degree of cellulose II crystallinity, which is determined to be set by the miscibility of the coagulant medium (nonsolvent) and the aqueous alkali cellulose solvent rather than the nonsolvents' polarity. This article provides an insight, thus creating a possibility to carefully tune and control the cellulose material properties when tailor-made for different applications., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Noncrystalline cellulose-based gel beads were used as a model material to investigate the effect of osmotic stress on a cellulosic network. The gel beads were exposed to osmotic stress by immersion in solutions with different concentrations of high molecular mass dextran and the equilibrium dimensional change of the gel beads was studied using optical microscopy. The volume fraction of cellulose was calculated from the volume of the gel beads in dextran solutions and their dry content and the relation between the cellulose volume fraction and the total osmotic pressure was thus obtained. The results show that the contribution to the osmotic pressure from counterions increases the water-retaining capacity of the beads at high osmotic pressures but also that the main factor controlling the gel bead collapse at high osmotic strains is the resistance to the deformation of the polymer chain network within the beads. Furthermore, the osmotic pressure associated with the deformation of the polymer network, which counteracts the deswelling of the beads, could be fitted to the Wall model indicating that the response of the cellulose polymer networks was independent of the charge of the cellulose. The best fit to the Wall model was obtained when the Flory-Huggins interaction parameter (χ) of the cellulose-water system was set to 0.55-0.60, in agreement with the well-established insolubility of high molecular mass β-(1,4)-d-glucan polymers in water.

In this study, the use of cubosomes for topical delivery of the antimicrobial peptide (AMP) LL-37 was investigated. Topical delivery of AMPs is of great interest for treatment of skin infections caused by bacteria, such as Staphylococcus aureus. AMP containing cubosomes were produced by three different preparation protocols and compared: (i) pre-loading, where LL-37 was incorporated into a liquid crystalline gel, which thereafter was dispersed into nanoparticles, (ii) post-loading, where LL-37 was let to adsorb onto pre-formed cubosomes, and (iii) hydrotrope-loading, where LL-37 was incorporated during the spontaneously formed cubosomes in an ethanol/glycerol monooleate mixture. Particle size and size distribution were analyzed using dynamic light scattering (DLS), liquid crystalline structure by small angle x-ray scattering (SAXS) and release of LL-37 by a fluorescamine assay. Proteolytic protection of LL-37 as well as bactericidal effect after enzyme exposure was investigated. The skin irritation potential of cubosomes was examined by an in vitro epidermis model. Finally, the bacterial killing property of the cubosomes was examined by an ex vivo pig skin wound infection model with Staphylococcus aureus. Data showed that a high loading of LL-37 induced formation of vesicles in case of cubosomes prepared by sonication (pre-loading). No release of LL-37 was observed from the cubosomes, indicating strong association of the peptide to the particles. Proteolysis studies showed that LL-37 was fully protected against enzymatic attacks while associated with the cubosomes, also denoting strong association of the peptide to the particles. As a consequence, bactericidal effect after enzyme exposure remained, compared to pure LL-37 which was subjected to proteolysis. No skin irritation potential of the cubosomes was found, thus enabling for topical administration. The ex vivo wound infection model showed that LL-37 in pre-loaded cubosomes killed bacteria most efficient., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Nanoscale building blocks of many materials exhibit extraordinary mechanical properties due to their defect-free molecular structure. Translation of these high mechanical properties to macroscopic materials represents a difficult materials engineering challenge due to the necessity to organize these building blocks into multiscale patterns and mitigate defects emerging at larger scales. Cellulose nanofibrils (CNFs), the most abundant structural element in living systems, has impressively high strength and stiffness, but natural or artificial cellulose composites are 3-15 times weaker than the CNFs. Here, we report the flow-assisted organization of CNFs into macroscale fibers with nearly perfect unidirectional alignment. Efficient stress transfer from macroscale to individual CNF due to cross-linking and high degree of order enables their Young's modulus to reach up to 86 GPa and a tensile strength of 1.57 GPa, exceeding the mechanical properties of known natural or synthetic biopolymeric materials. The specific strength of our CNF fibers engineered at multiscale also exceeds that of metals, alloys, and glass fibers, enhancing the potential of sustainable lightweight high-performance materials with multiscale self-organization.

Hydrothermal treatments of birch wood and kraft pulp were compared for their ability to extract the xylan and produce viscose-grade pulp. Water post-hydrolysis of kraft pulp produced a high-purity cellulosic pulp with lower viscosity but higher cellulose yield than traditional pre-hydrolysis kraft pulping of wood. Post-hydrolysis of pulp also increased the crystallite dimensions and degree of crystallinity in cellulose, and promoted a higher extent of fibril aggregation. The lower specific surface area in post-hydrolyzed pulps, derived from their larger fibril aggregates, decreased the accessibility of OH groups. However, this lower accessibility did not seem to decrease the pulp reactivity to derivatizing chemicals. In the aqueous side-stream, the xylose yield was similar in both pre- and post-hydrolysates, although conducting post-hydrolysis of pulp in a flow-through system enabled the recovery of high purity and molar mass (∼10 kDa) xylan for high-value applications., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Macroscopic beads of water-based gels consisting of uncharged and partially charged β-(1,4)-d-glucan polymers were developed to be used as a novel model material for studying the water induced swelling of the delignified plant fiber walls. The gel beads were prepared by drop-wise precipitation of solutions of dissolving grade fibers carboxymethylated to different degrees. The internal structure was analyzed using Solid State Cross-Polarization Magic Angle Spinning Carbon-13 Nuclear Magnetic Resonance and Small Angle X-ray Scattering showing that the internal structure could be considered a homogeneous, non-crystalline and molecularly dispersed polymer network. When beads with different charge densities were equilibrated with aqueous solutions of different ionic strengths and/or pH, the change in water uptake followed the trends expected for weak polyelectrolyte gels and the trends found for cellulose-rich fibers. When dried and subsequently immersed in water the beads also showed an irreversible loss of swelling depending on the charge and type of counter-ion which is commonly also found for cellulose-rich fibers. Taken all these results together it is clear that the model cellulose-based beads constitute an excellent tool for studying the fundamentals of swelling of cellulose rich plant fibers, aiding in the elucidation of the different molecular and supramolecular contributions to the swelling., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: To describe early radiographic findings in patients from the Swedish psoriatic arthritis (SwePsA) registry, progression of destruction, correlations with clinical disease variables, and predictors of destruction., Methods: Hand and foot radiographs were available for 72 of 197 SwePsA patients followed for 5 years. Clinical data were collected according to the SwePsA protocol., Results: Disease characteristics and clinical improvement were similar in men and women. Radiographic abnormalities were more pronounced in men. Total Wassenberg radiographic score at baseline was 0 in 45% of men and 51% of women. One man and one woman had a score > 10. At 5 years, total score was 0 in 14% of men and 40% of women (p = 0.018); 17% of men and 7% of women had scores > 10. Mean total scores for men and women had increased. Baseline erythrocyte sedimentation rate was associated with baseline total radiographic score. In men, swollen joint count was positively, and in women tender joint count negatively, correlated to total radiographic score. After 5 years, only male scores, mainly hand scores, significantly correlated with 28-joint Disease Activity Score and Disease Activity Index for Psoriatic Arthritis scores, swollen joint count, and dactylitis. Achieving remission or minimal disease activity after 5 years protected against structural damage, mainly in men., Conclusion: Radiographic progression in early PsA was generally slow but substantial. Male sex appears to be a risk factor for early radiographic damage while the presence of baseline radiographic damage and dactylitis developing during followup seem to predict further destruction. Hand and foot radiograph scoring cannot be substituted with clinical signs.

Cellulose from wood fibers can be modified for use in flame-retardant composites as an alternative to halogen-based compounds. For this purpose, sulfite dissolving pulp fibers have been chemically modified by phosphorylation, and the resulting material has been used to prepare cellulose nanofibrils (CNF) that have a width of approximately 3 nm. The phosphorylation was achieved using (NH4)2HPO4 in the presence of urea, and the degree of substitution by phosphorus was determined by X-ray photoelectron spectroscopy, conductometric titration, and nuclear magnetic resonance spectroscopy. The presence of phosphate groups in the structure of CNF has been found to noticeably improve the flame retardancy of this material. The nanopaper sheets prepared from phosphorylated CNF showed self-extinguishing properties after consecutive applications of a methane flame for 3 s and did not ignite under a heat flux of 35 kW/m2, as shown by flammability and cone calorimetry measurements, respectively.

Background: Lignocellulosic substrates and pulping process streams are of increasing relevance to biorefineries for second generation biofuels and biochemical production. They are known to be rich in sugars and inhibitors such as phenolic compounds, organic acids and furaldehydes. Phenolic compounds are a group of aromatic compounds known to be inhibitory to fermentative organisms. It is known that inhibition of Sacchromyces cerevisiae varies among phenolic compounds and the yeast is capable of in situ catabolic conversion and metabolism of some phenolic compounds. In an approach to engineer a S. cerevisiae strain with higher tolerance to phenolic inhibitors, we selectively investigated the metabolic conversion and physiological effects of coniferyl aldehyde, ferulic acid, and p-coumaric acid in Saccharomyces cerevisiae. Aerobic batch cultivations were separately performed with each of the three phenolic compounds. Conversion of each of the phenolic compounds was observed on time-based qualitative analysis of the culture broth to monitor various intermediate and final metabolites., Result: Coniferyl aldehyde was rapidly converted within the first 24 h, while ferulic acid and p-coumaric acid were more slowly converted over a period of 72 h. The conversion of the three phenolic compounds was observed to involved several transient intermediates that were concurrently formed and converted to other phenolic products. Although there were several conversion products formed from coniferyl aldehyde, ferulic acid and p-coumaric acid, the conversion products profile from the three compounds were similar. On the physiology of Saccharomyces cerevisiae, the maximum specific growth rates of the yeast was not affected in the presence of coniferyl aldehyde or ferulic acid, but it was significantly reduced in the presence of p-coumaric acid. The biomass yields on glucose were reduced to 73 and 54 % of the control in the presence of coniferyl aldehyde and ferulic acid, respectively, biomass yield increased to 127 % of the control in the presence of p-coumaric acid. Coniferyl aldehyde, ferulic acid and p-coumaric acid and their conversion products were screened for inhibition, the conversion products were less inhibitory than coniferyl aldehyde, ferulic acid and p-coumaric acid, indicating that the conversion of the three compounds by Saccharomyces cerevisiae was also a detoxification process., Conclusion: We conclude that the conversion of coniferyl aldehyde, ferulic acid and p-coumaric acid into less inhibitory compounds is a form of stress response and a detoxification process. We hypothesize that all phenolic compounds are converted by Saccharomyces cerevisiae using the same metabolic process. We suggest that the enhancement of the ability of S. cerevisiae to convert toxic phenolic compounds into less inhibitory compounds is a potent route to developing a S. cerevisiae with superior tolerance to phenolic compounds.

Background: The efficiency of enzymatic hydrolysis is reduced by the structural properties of cellulose. Although efforts have been made to explain the mechanism of enzymatic hydrolysis of cellulose by considering the interaction of cellulolytic enzymes with cellulose or the changes in the structure of cellulose during enzymatic hydrolysis, the process of cellulose hydrolysis is not yet fully understood. We have analysed the characteristics of the complex supramolecular structure of cellulose on the nanometre scale in terms of the spatial distribution of fibrils and fibril aggregates, the accessible surface area and the crystallinity during enzymatic hydrolysis. Influence of the porosity of the substrates and the hydrolysability was also investigated. All cellulosic substrates used in this study contained more than 96% cellulose., Results: Conversion yields of six cellulosic substrates were as follows, in descending order: nano-crystalline cellulose produced from never-dried soda pulp (NCC-OPHS-ND) > never-dried soda pulp (OPHS-ND) > dried soda pulp (OPHS-D) > Avicel > cotton treated with sodium hydroxide (cotton + NaOH) > cotton., Conclusions: No significant correlations were observed between the yield of conversion and supramolecular characteristics, such as specific surface area (SSA) and lateral fibril dimensions (LFD). A strong correlation was found between the average pore size of the starting material and the enzymatic conversion yield. The degree of crystallinity was maintained during enzymatic hydrolysis of the cellulosic substrates, contradicting previous explanations of the increasing crystallinity of cellulose during enzymatic hydrolysis. Both acid and enzymatic hydrolysis can increase the LFD, but no plausible mechanisms could be identified. The sample with the highest initial degree of crystallinity, NCC-OPHS-ND, exhibited the highest conversion yield, but this was not accompanied by any change in LFD, indicating that the hydrolysis mechanism is not based on lateral erosion.

The industrial production of cellulolytic enzymes is dominated by the filamentous fungus Trichoderma reesei (anamorph of Hypocrea jecorina). In order to develop optimal enzymatic cocktail, it is of importance to understand the natural regulation of the enzyme profile as response to the growth substrate. The influence of the complexity of cellulose on enzyme production by the microorganisms is not understood. In the present study we attempted to understand how different physical and structural properties of cellulose-rich substrates affected the levels and profiles of extracellular enzymes produced by T. reesei. Enzyme production by T. reesei Rut C-30 was studied in submerged cultures on five different cellulose-rich substrates, namely, commercial cellulose Avicel® and industrial-like cellulosic pulp substrates which consist mainly of cellulose, but also contain residual hemicellulose and lignin. In order to evaluate the hydrolysis of the substrates by the fungal enzymes, the spatial polymer distributions were characterised by cross-polarisation magic angle spinning carbon-13 nuclear magnetic resonance (CP/MAS (13)C-NMR) in combination with spectral fitting. Proteins in culture supernatants at early and late stages of enzyme production were labeled by Tandem Mass Tags (TMT) and protein profiles were analysed by liquid chromatography-tandem mass spectrometry. The data have been deposited to the ProteomeXchange with identifier PXD001304. In total 124 proteins were identified and quantified in the culture supernatants, including cellulases, hemicellulases, other glycoside hydrolases, lignin-degrading enzymes, auxiliary activity 9 (AA9) family (formerly GH61), supporting activities of proteins and enzymes acting on cellulose, proteases, intracellular proteins and several hypothetical proteins. Surprisingly, substantial differences in the enzyme profiles were found even though there were minor differences in the chemical composition between the cellulose-rich substrates., (Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.)

We demonstrate how to prepare extraordinarily deformable, gas-filled, spherical capsules from nonmodified cellulose. These capsules have a low nominal density, ranging from 7.6 to 14.2 kg/m(3), and can be deformed elastically to 70% deformation at 50% relative humidity. No compressive strain-at-break could be detected for these dry cellulose capsules, since they did not rupture even when compressed into a disk with pockets of highly compressed air. A quantitative constitutive model for the large deformation compression of these capsules is derived, including their high-frequency mechanical response and their low-frequency force relaxation, where the latter is governed by the gas barrier properties of the dry capsule. Mechanical testing corroborated these models with good accuracy. Force relaxation measurements at a constant compression rendered an estimate for the gas permeability of air through the capsule wall, calculated to 0.4 mL μm/m(2) days kPa at 50% relative humidity. These properties taken together open up a large application area for the capsules, and they could most likely be used for applications in compressible, lightweight materials and also constitute excellent model materials for adsorption and adhesion studies.

Objective: The Swedish Early Psoriatic Arthritis Register describes the course of early psoriatic arthritis (PsA) in a real life clinical setting in Sweden. The aim of this study was to obtain information on predictors of clinical outcomes over a 5-year period with special focus on effects of gender, joint patterns, diagnostic delay and initial disease activity., Methods: In six centres, patients with signs suggestive of PsA were included in the Swedish Early Psoriatic Arthritis Register within 2 years of symptom onset. CASPAR (classification for psoriatic arthritis) criteria were fulfilled by 197 patients who had passed the 5-year follow-up. Disease activity was measured by the Disease Activity Score including 28 joints (DAS28) and the Disease Activity Index for Psoriatic Arthritis (DAPSA). Remission and minimal disease activity (MDA) were used as outcome measures., Results: Mean age at inclusion was 46 years, younger in male than female patients (43 vs 48 years). Mean DAS28 was 3.7 and 3.0 at inclusion and 2.8 and 2.1 at follow-up for women and men, respectively-significantly higher in women at both visits. Likewise, DAPSA scores were significantly higher in women. The degree of improvement (change in DAS28 and DAPSA) was similar. Men achieved MDA or remission (50% vs 33%, 25% vs 13%, respectively) more often, and women had significantly more polyarthritis at inclusion (49% vs 27%) and after 5 years (25% vs 15%). Axial or mono/oligoarticular disease was predominant in men. Independent predictors of MDA at the 5-year follow-up were: shorter symptom duration; greater general well-being (global visual analogue scale); and low Health Assessment Questionnaire at inclusion., Conclusions: In early PsA, short delay between onset of symptoms and diagnosis, preserved function, and male gender are the most important predictors of favourable clinical outcome at the 5-year follow-up. Early recognition of PsA and active treatment may be important, particularly in women with polyarticular disease.

Dry ultra-porous cellulose fibres were obtained using a liquid exchange procedure in which water was replaced in the following order: water, methanol, acetone, and finally pentane; thereafter, the fibres were dried with Ar(g). The dry samples (of TEMPO-oxidized dissolving pulp) had a specific surface area of 130 m(2)g(-1) as measured using BET nitrogen gas adsorption. The open structure in the dry state was also revealed using field emission scanning electron microscopy. This dry open structure was used as a scaffold for in situ polymerization. Both poly(methyl methacrylate) and poly(butylacrylate) were successfully used as matrix polymers for the composite material (fibre/polymer), comprising approximately 20 wt% fibres. Atomic force microscopy phase imaging indicated a nanoscale mixing of the matrix polymer and the cellulose fibril aggregates and this was also supported by mechanical testing of the prepared composite where the open fibre structure produced superior composites. The fibre/polymer composite had a significantly reduced water absorption capacity also indicating an efficient filling of the fibre structure with the matrix polymer., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

We investigated the association between cigarette smoking and the risk of developing rheumatoid arthritis (RA) in the Malaysian population. A total of 1,056 RA patients and 1,416 matched controls aged 18-70 years within a defined area of Peninsular Malaysia were evaluated in a case-control study between August 2005 and December 2009. A case was defined as a person with early diagnosed RA using the 1987 American College of Rheumatology criteria for RA. Controls were randomly selected matched for sex, age, and residential area. Cases and controls answered a questionnaire on a broad range of issues, including lifestyle factors and smoking habits wherein current and former smoking was classified as ever-smoking. The presence of anti-citrullinated peptide antibodies (ACPA) was determined for cases and controls. We found that ever-smokers had an increased risk of developing ACPA-positive RA [odds ratio (OR) = 4.1, 95% confidence interval (CI) 1.9-9.2] but not ACPA-negative RA (OR = 0.7, 95% CI 0.3-2.0), compared with never-smokers. A significant dose-response relationship between cumulative dose of smoking and risk of ACPA-positive RA was observed (<20 pack-years OR = 3.3, 95% CI 1.1-9.8; at least 20 pack-years OR = 5.2, 95% CI 1.6-17.6). Hence, smoking is associated with an increased risk of ACPA-positive RA in the Malaysian population, in which the genetic context is similar to several other Asian countries.

Introduction: Rheumatoid arthritis (RA) is a multifactorial autoimmune disease in which genetic and environmental factors interact in the etiology. In this study, we investigated whether smoking and HLA-DRB1 shared-epitope (SE) alleles interact differently in the development of the two major subgroups of rheumatoid arthritis (RA), anti-citrullinated proteins antibody (ACPA)-positive and ACPA-negative disease, in a multiethnic population of Asian descent., Methods: A case-control study comprising early diagnosed RA cases was carried out in Malaysia between 2005 and 2009. In total, 1,076 cases and 1,612 matched controls participated in the study. High-resolution HLA-DRB1 genotyping was performed for shared-epitope (SE) alleles. All participants answered a questionnaire on a broad range of issues, including smoking habits. The odds ratio (OR) of developing ACPA-positive and ACPA-negative disease was calculated for smoking and the presence of any SE alleles separately. Potential interaction between smoking history (defined as "ever" and "never" smoking) and HLA-DRB1 SE alleles also was calculated., Results: In our multiethnic study, both the SE alleles and smoking were associated with an increased risk of developing ACPA-positive RA (OR SE alleles, 4.7; 95% confidence interval (CI), 3.6 to 6.2; OR smoking, 4.1; 95% CI, 1.9 to 9.2). SE-positive smokers had an odds ratio of ACPA-positive RA of 25.6 (95% CI, 10.4 to 63.4), compared with SE-negative never-smokers. The interaction between smoking and SE alleles was significant (attributable proportion due to interaction (AP) was 0.7 (95% CI, 0.5 to 1.0)). The HLA-DRB1*04:05 SE allele, which is common in Asian populations, but not among Caucasians, was associated with an increased risk of ACPA-positive RA, and this allele also showed signs of interaction with smoking (AP, 0.4; 95% CI, -0.1 to 0.9). Neither smoking nor SE alleles nor their combination was associated with an increased risk of ACPA-negative RA., Conclusions: The risk of developing ACPA-positive RA is associated with a strong gene-environment interaction between smoking and HLA-DRB1 SE alleles in a Malaysian multiethnic population of Asian descent. This interaction seems to apply also between smoking and the specific HLA-DRB1*04:05 SE allele, which is common in Asian populations but not in Caucasians.

Regulatory T cells (Tregs) are important for maintaining immune homeostasis, but many studies suggest that Tregs are functionally impaired in autoimmune and chronic inflammatory disorders. In addition, effector T cells may vary in sensitivity toward Treg suppression. Herein, we have studied the interplay between T effectors and Tregs in the rheumatic joint. Synovial Tregs demonstrated a high degree of FOXP3 demethylation and displayed only marginal IL-17 and virtually no IFN-γ production following in vitro stimulation, altogether indicating suppressive capacity. Still, the frequency of FOXP3 expression could not predict the degree of suppression. Instead, the inflammatory milieu in the joint, i.e. proliferative capacity of effector T cells and in situ levels of pro-inflammatory cytokines influenced Treg function. Indeed, blocking IL-6 or TNF increased the suppression by Tregs in co-cultures. Additionally, approximately 30% of the synovial FOXP3(+) T cells were Ki67(+) and hence actively dividing, but proliferation did not overlap with cytokine production, suggesting that these cells represent functional Tregs having met their cognate antigen and expanded in an attempt to alleviate joint inflammation. Overall, our data argue against a general functional deficit in joint-derived Tregs and instead emphasize the importance of the inflammatory milieu to set the threshold for immune regulation., (Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: To investigate the associations between HLA-DRB1 shared epitope (SE) alleles and rheumatoid arthritis in subsets of rheumatoid arthritis defined by autoantibodies in three Asian populations from Malaysia., Methods: 1,079 rheumatoid arthritis patients and 1,470 healthy controls were included in the study. Levels of antibodies to citrullinated proteins (ACPA) and rheumatoid factors were assessed and the PCR-SSO method was used for HLA-DRB1 genotyping., Results: The proportion of ACPA positivity among Malay, Chinese and Indian rheumatoid arthritis patients were 62.9%, 65.2% and 68.6%, respectively. An increased frequency of SE alleles was observed in ACPA-positive rheumatoid arthritis among the three Asian ethnic groups. HLA-DRB1*10 was highly associated with rheumatoid arthritis susceptibility in these Asian populations. HLA-DRB1*0405 was significantly associated with susceptibility to rheumatoid arthritis in Malays and Chinese, but not in Indians. HLA-DRB1*01 did not show any independent effect as a risk factor for rheumatoid arthritis in this study and HLA-DRB1*1202 was protective in Malays and Chinese. There was no association between SE alleles and ACPA- negative rheumatoid arthritis in any of the three Asian ethnic groups., Conclusion: The HLA-DRB1 SE alleles increase the risk of ACPA-positive rheumatoid arthritis in all three Asian populations from Malaysia.

A sequence of treatments consisting of an initial xylanase treatment followed by cold alkaline extraction and a final endoglucanase treatment was investigated as a process for upgrading non-wood paper-grade pulps to dissolving-grade pulps for viscose production. Five commercial dried bleached non-wood soda/AQ paper pulps, from flax, hemp, sisal, abaca, and jute, were studied for this purpose. Commercial dried bleached eucalyptus dissolving pulp was used as reference sample. Sisal pulp showed the highest improvement in Fock's reactivity, reaching levels nearly as high or even higher than that of eucalyptus dissolving pulp (65%), and a low hemicellulose content (3-4%) when was subjected to this sequence of treatments. The viscosity, however, decreased considerably. A uniform and narrow molecular weight distribution was observed by size exclusion chromatography. (13)C nuclear magnetic resonance spectroscopy and Raman microspectroscopy revealed that the cellulose structure consisted of cellulose I., (Copyright 2010 Elsevier Ltd. All rights reserved.)

X-ray diffraction, scanning electron microscopy (SEM), and solid-state cross-polarization magic-angle-spinning (CP/MAS) (13)C-NMR spectroscopy were applied to determine changes over time in the morphology and crystallinity of lime wood (Tilia cordata Miller) generated by the soft-rot fungi. Wood samples were inoculated with Trichoderma viride Pers for various durations up to 84 days. Structural and morphological modifications were assessed by comparing the structural features of decayed lime wood samples with references. Significant morphology changes such as defibration or small cavities were clearly observed on the SEM micrographs of lime wood samples exposed to fungi. Following the deconvolution process of the diffraction patterns, the degree of crystallinity, apparent lateral crystallite size, the proportion of crystallite interior chains, and the cellulose fraction have been determined. It was found that all crystallographic data vary with the duration of exposure to fungi. The degree of crystallinity and cellulose fraction tend to decrease, whereas the apparent lateral crystallite size and the proportion of crystallite interior chains increase with prolonged biodegradation processes. The most relevant signals in CP/MAS (13)C-NMR spectra were assigned according to literature data. The differences observed were discussed in terms of lignin and cellulose composition: by fixing the lignin reference signal intensity, the cellulose and hemicelluloses moieties showed a relative decrease compared to the lignin signals in decayed wood.

CP/MAS (13)C NMR spectroscopy was used in combination with spectral fitting to examine the surface structure of hydrated cellulose I fibrils from Halocynthia and Gluconoacetobacter xylinus. To increase the spectral intensities and minimize signal overlap, G. xylinus celluloses site-specifically enriched in (13)C either on C4 or on both C1 and C6 were examined. The experimental data showed multiple C4 and C6 signals for the water accessible fibril surfaces in the highly crystalline celluloses. These signal multiplicities were attributed to structural features in the surface layers induced by the fibril interior, and could not be extracted by spectral fitting in celluloses with a lower degree of crystallinity such as cellulose from cotton., (Copyright 2009 Elsevier Ltd. All rights reserved.)

Objective: Patients with symptoms and signs compatible with psoriatic arthritis (PsA), with or without psoriasis, have been documented in the Swedish Early Psoriatic Arthritis (SwePsA) register. Our aim was to find markers for disease progression and to evaluate treatments for PsA using these data., Methods: Patients referred to rheumatology outpatient clinics within 2 years of onset were assessed on inclusion and at followup 2 years later. Data collection was performed according to the program for SwePsA, and classification was as described by Moll and Wright and the ClASsification Criteria for Psoriatic ARthritis (CASPAR). Remission was recorded if the patient had no tender or swollen joints and if erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were within the reference range. Patients with early rheumatoid arthritis (RA) recruited from the Swedish Early Rheumatoid Arthritis Register (Ramona) provided comparison data., Results: One hundred thirty-five patients with PsA according to CASPAR were assessed; 44% were classified as having mono/oligoarthritis and 47% as polyarthritis. Two patients (1%) were in remission initially, and 23 (17%) at followup. Patients with polyarticular disease had the highest inflammatory activity, measured by swollen and tender joint counts, ESR, Health Assessment Questionnaire, and self-assessment by visual analog scale of pain and global disease activity. Dactylitis was associated with radiological findings. Compared with RA patients, they had significantly lower CRP, ESR, and number of swollen joints (p = 0.0003, p = 0.0026, p = 0.0380, respectively) at inclusion, but equal numbers of tender joints and self-assessment of pain and disease activity., Conclusion: About half the patients had polyarthritis and the other half had mono/oligoarthritis at followup after 2 years. Patients with polyarthritis had the highest inflammatory activity. Apart from ESR, CRP, and swollen joint count, there were no significant differences in activity between RA and polyarticular PsA.

Solid-state nuclear magnetic resonance (CP/MAS 13C NMR) spectroscopy has often been used to study cellulose structure, but some features of the cellulose NMR spectrum are not yet fully understood. One such feature is a doublet around 84 ppm, a signal that has been proposed to originate from C4 atoms at cellulose fibril surfaces. The two peaks yield different T1, differing by approximately a factor of 2 at 75 MHz. In this study, we calculate T1 from C4-H4 vector dynamics obtained from molecular dynamics computer simulations of cellulose I beta-water interfacial systems. Calculated and experimentally obtained T1 values for C4 atoms in surface chains fell within the same order of magnitude, 3-20 s. This means that the applied force field reproduces relevant surface dynamics for the cellulose-water interface sufficiently well. Furthermore, a difference in T1 of about a factor of 2 in the range of Larmor frequencies 25-150 MHz was found for C4 atoms in chains located on top of two different crystallographic planes, namely, (110) and (10). A previously proposed explanation that the C4 peak doublet could derive from surfaces parallel to different crystallographic planes is herewith strengthened by computationally obtained evidence. Another suggested basis for this difference is that the doublet originates from C4 atoms located in surface anhydro-glucose units with hydroxymethyl groups pointing either inward or outward. This was also tested within this study but was found to yield no difference in calculated T1.

This case report presents the clinical and radiographic course of temporomandibular joint (TMJ) involvement in a patient with severe TMJ symptoms from psoriatic arthritis (PsA) resistant to both systemic infliximab and intra-articular glucocorticoid and who therefore received multiple intra-articular infliximab injections for 36 weeks. TMJ symptoms improved after the first bilateral intra-articular infliximab injections but even more so after the second injections. The considerable improvement remained for the 36 weeks studied. Bilateral computerized tomography showed no progression in radiographic changes during the treatment. No adverse reaction was observed from the intra-articular injections.

Background: Inflammation is a major contributor to atherosclerotic vascular disease. Inflammatory parameters such as C-reactive protein (CRP) and Interleukin-6 (IL-6) have been shown to be strong predictors of cardiovascular events. The association between preoperative inflammatory parameters and early graft occlusion as well as cardiovascular events after coronary artery bypass grafting (CABG) has not, however, been fully elucidated. The aims of the present study were to prospectively investigate the prognostic value of the inflammatory parameters IL-6, CRP, and endothelin (ET-1) to predict early graft occlusion as well as late cardiovascular events after CABG., Methods: In the present study 99 patients undergoing CABG because of stable angina pectoris due to significant coronary artery disease were prospectively included. Coronary angiography was repeated 3 months after CABG in 81 patients in order to evaluate early graft occlusion. Blood samples were collected before CABG in all patients. Patients were followed up for a median of 5 (3-7) years after CABG., Results: Twenty-five patients (31%) had one or more occluded grafts at the 3-month control coronary angiography. The patients with occluded grafts had higher preoperative CRP and IL-6 levels in plasma [CRP 2.22 (1.11-4.47) mg/L vs. 1.23 (0.71-2.27) mg/L P=0.03] and [IL-6 2.88 (1.91-5.94) pg/mL vs. 2.15 (1.54-3.14) pg/mL P=0.006]. There were 23 late cardiovascular events among the 99 patients during the follow-up. Patients experiencing late cardiovascular events had higher preoperative IL-6 levels than those without late cardiovascular events [4.13 (1.83-5.87) pg/mL vs. 2.08 (1.53-2.29) pg/mL, P=0.002] whereas CRP levels did not differ significantly between the two groups [1.5 (0.79-4.41) mg/L vs. 1.33 (0.74-2.48) mg/L, P=0.41]. Looking at IL-6, a cut off value more than 3.8 pg/ml was associated with a significant higher risk for an early graft occlusion (P=0.04) and late cardiovascular events (P=0.00003). Preoperative endothelin-1 did not predict early graft occlusions or late cardiovascular events., Conclusions: Raised preoperative IL-6 levels are predictors of both early graft occlusion and late cardiovascular events after CABG. Elevated preoperative CRP levels can predict early graft occlusion after CABG. Endothelin did not differ between the two groups.

Toward exploiting the attractive mechanical properties of cellulose I nanoelements, a novel route is demonstrated, which combines enzymatic hydrolysis and mechanical shearing. Previously, an aggressive acid hydrolysis and sonication of cellulose I containing fibers was shown to lead to a network of weakly hydrogen-bonded rodlike cellulose elements typically with a low aspect ratio. On the other hand, high mechanical shearing resulted in longer and entangled nanoscale cellulose elements leading to stronger networks and gels. Nevertheless, a widespread use of the latter concept has been hindered because of lack of feasible methods of preparation, suggesting a combination of mild hydrolysis and shearing to disintegrate cellulose I containing fibers into high aspect ratio cellulose I nanoscale elements. In this work, mild enzymatic hydrolysis has been introduced and combined with mechanical shearing and a high-pressure homogenization, leading to a controlled fibrillation down to nanoscale and a network of long and highly entangled cellulose I elements. The resulting strong aqueous gels exhibit more than 5 orders of magnitude tunable storage modulus G' upon changing the concentration. Cryotransmission electron microscopy, atomic force microscopy, and cross-polarization/magic-angle spinning (CP/MAS) 13C NMR suggest that the cellulose I structural elements obtained are dominated by two fractions, one with lateral dimension of 5-6 nm and one with lateral dimensions of about 10-20 nm. The thicker diameter regions may act as the junction zones for the networks. The resulting material will herein be referred to as MFC (microfibrillated cellulose). Dynamical rheology showed that the aqueous suspensions behaved as gels in the whole investigated concentration range 0.125-5.9% w/w, G' ranging from 1.5 Pa to 105 Pa. The maximum G' was high, about 2 orders of magnitude larger than typically observed for the corresponding nonentangled low aspect ratio cellulose I gels, and G' scales with concentration with the power of approximately three. The described preparation method of MFC allows control over the final properties that opens novel applications in materials science, for example, as reinforcement in composites and as templates for surface modification.

Objective: The aim of this study was to prospectively investigate changes in brain natriuretic peptide (BNP) and amino terminal pro-BNP (NT-pro-BNP) in relation to functional status after surgical ventricular restoration (SVR)., Methods: Between March 2003 and May 2006, 29 patients (20 men and 9 women, mean age 65 years, mean ejection fraction 24%) with post-infarction left ventricular aneurysm and depressed left ventricular function underwent SVR according to the Dor technique at our institution. Twenty-two patients (76%) were in New York heart association (NYHA) functional class III or IV. Multi-vessel disease was present in 26 patients. Natriuretic peptides, functional status, ejection fraction and left ventricular volumes were analyzed at baseline, after 6 months, and late postoperatively., Results: There was no early mortality. Survival at 24 months was 93%. Six months postoperatively 25/29 (86%) patients were in NYHA class I and II (p<0.001) and at late (mean 21 months) follow-up, all patients were in NYHA class I and II. There was a persistent reduction of NT-pro-BNP (2406 pg/ml vs 1510 pg/ml; p=0.03 and 975 pg/ml; p=0.03) and BNP (312 pg/ml vs 228 pg/ml; p=0.12 and 191 pg/ml; p=0.20) 6 months postoperatively and at late follow-up, respectively. Ejection fraction improved from 24% to 37% (p<0.001) at 6 months. End-diastolic (110 ml/m(2) vs 90 ml/m(2), p=0.009) and end-systolic (75 ml/m(2) vs 52 ml/m(2), p=0.006) volume index were reduced at 6 months. Functional improvement correlated significantly with reduction in BNP (r=0.61, p=0.01) and NT-pro-BNP (r=0.58, p=0.003) 6 months after surgery. Ejection fraction correlated inversely with BNP (r=-0.58, p=0.02) and NT-pro-BNP (r=-0.51, p=0.04), and end-systolic volume correlated with BNP (r=0.65, p=0.03) and NT-pro-BNP (r=0.62, p=0.03) 6 months after surgery., Conclusions: Heart failure secondary to post-infarction left ventricular remodeling can be reversed by SVR. Improvement in these patients was associated with reduced levels of B-type natriuretic peptides 6 months after surgery. Clinical improvement was maintained and peptide levels were further reduced at late follow-up.

Polydimethyldiallylammonium chloride (PDADMAC) and polystyrene sulfonate (PSS) have been used to build-up polyelectrolyte multilayers (PEMs) on chemical soft wood fibres and on SiO2 at various electrolyte concentrations. Adsorption onto SiO2 was studied using a stagnation point adsorption reflectometer (SPAR), and the adsorbed amount of PDADMAC and PSS on the fibres was determined using nitrogen analysis and Schöniger burning, respectively. The adsorption onto the two substrates was then compared. Paper testing showed that the tensile index (TI) increased by about 90% when 11 layers had been adsorbed, and that there was a correlation between the adsorbed amount and the increase in TI. It was also shown that the particular polymer present in the outermost layer significantly influenced the TI, and that PDADMAC produced a higher TI. A correlation between the adsorbed amount and the TI was also found. Individual fibres were partly treated with a PEM and analysed using a dynamic contact angle analyser (DCA) and environmental scanning electron microscopy (ESEM).

The CP/MAS (13)C NMR line shape of cellulose I has been qualitatively analyzed by direct simulations using the Ornstein-Uhlenbeck stochastic process and the Kubo model. Both approaches describe a anhydroglucose C4 carbon as a oscillator with fluctuating Larmor frequency. The NMR resonance frequency is written omega=omega +omega(t), where the fluctuating part with zero mean was modelled as a stationary Markov diffusion process. The simulation results both motivates the use of multiple line shapes when fitting CP/MAS (13)C NMR spectra recorded on cellulose I and gives some insights into why signals from crystalline cellulose I give rise to Lorentzian line shapes.

Aim: The role of inflammation in atherothrombotic disorders is becoming increasingly recognized. The present study prospectively investigates relationships between inflammatory markers and hemostatic variables, and non-invasive measures of carotid artery atherosclerosis., Methods: Markers of hemostasis (sP-selectin and fibrinogen), cytokines (IL-6, IL-8, TNF-a and MCP-1), inflammatory variables (hsCRP, SAA and calprotectin) and cell adhesion molecules (ICAM-1 and VCAM-1) as well as ultrasonography of the carotid arteries were assessed in 111 consecutive outpatients with manifest or suspected coronary artery disease (CAD)., Results: Thirty-eight patients with manifest cardiovascular disease had higher IL-6 (P < 0.01) but not hsCRP levels. Higher levels of IL-6, calprotectin and VCAM-1 (all P < 0.05) were found in 35 patients with carotid plaques. In the whole study population (n = 109) an increased common carotid artery lumen diameter (LD) and cross sectional intima-media area (CIMA) was related to higher IL-6, IL-8 and MCP-1 levels (all P < 0.05), and increased LD also to higher hsCRP, calprotectin (both P < 0.05), sP-selectin and fibrinogen levels (both P < 0.01). Both LD and CIMA were related to VCAM-1 (both P < 0.01), but not to ICAM-1 levels. The intima-media thickness of the carotid artery was only positively related to MCP-1 levels (P < 0.05). Only the relation between IL-6 and LD remained significant after adjustment for age, gender, body mass index, smoking status or present lipid-lowering treatment., Conclusions: Several biomarkers of inflammation are related to ultrasonographic measures of carotid artery atherosclerosis in patients with moderate to high prevalence of CAD. IL-6 seems to be an independent and useful biomarker of atherosclerosis in this group of patients.

Increased intima-media thickness (IMT) in the common carotid artery (CCA) correlates with conventional risk factors for cardiovascular disease and is an independent predictor of cardiac events. However, correlation between IMT and degree of ischemic heart disease evaluated by coronary angiogram is weak. The purpose of this study was to investigate the relationship between measures of carotid atherosclerosis and the extent and severity of coronary artery disease (CAD) in 111 consecutive patients (60 men and 51 women, mean age 60 years) with known or suspected CAD who were investigated with adenosine-stress myocardial perfusion scintigraphy. Common carotid artery lumen diameter (LD) and IMT of the carotid bulb and distal CCA were measured with ultrasound, and CCA cross-sectional intima-media area (CIMA) was calculated. Seventy-two of 110 patients (65%) had significant perfusion defects. Increasing carotid plaque occurrence (absence, unilateral or bilateral occurrence) correlated with more advanced CAD (p<0.01). The extent and severity of myocardial hypoperfusion correlated significantly with presence of carotid plaque (r=0.23 and 0.24 respectively, p<0.05), CIMA (r=0.23 and 0.22, p<0.05), and LD (r<0.26 and 0.25, p<0.01) but not with IMT. In contrast to CIMA, LD failed to show an independent relation to extent of CAD after adjustment for age, sex, and body mass index. In conclusion, in subjects with intermediate to high risk of ischemic heart disease, occurrence of carotid plaques and increased cross-sectional intimamedia area in the common carotid artery are the best parameters for predicting CAD expressed as myocardial hypoperfusion.

The distribution of 4-O-methylglucuronic acid residues along the polysaccharide chains of xylans isolated from birch, aspen, spruce, pine, and larch was studied here employing matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) analysis of the oligosaccharide mixtures obtained by partial acid hydrolysis. The hydrolyzates thus obtained were analyzed by MALDI-MS or by capillary electrophoresis as well as by size exclusion chromatography in combination with MALDI-MS. In the case of all softwood xylans examined, the major portion of the 4-O-methylglucuronic acid residues were distributed regularly on every seventh or eighth xylose residue, while a minor portion of these residues were attached to adjacent xylose residues in the beta-(1-->4)-D-xylopolysaccharide chains. In contrast, the 4-O-methylglucuronic acid residues in the hardwood xylans examined were found to be distributed irregularly within the xylan. Further support for these experimental findings with the xylans was obtained by simulation of the distribution patterns of the molecular masses of oligosaccharides arising from polysaccharides with the postulated distribution of uronic acid residues.

The present study was undertaken to evaluate the effects of an intravenous infusion of angiotensin II (10 ng/kg per min) on platelet function and coagulation in vivo in 18 healthy males. The infusion increased mean arterial pressure by 23+/-2 mm Hg. Plasma beta-thromboglobulin levels, reflecting platelet secretion, increased by 66+/-24% during the infusion, as did also platelet surface expression of P-selectin as measured by flow cytometry. Platelet fibrinogen binding increased, whereas platelet aggregability, assessed by ex vivo filtragometry, was unaltered. Angiotensin II caused mild activation of the coagulation cascade with increases in plasma levels of thrombin-antithrombin complex and prothrombin fragment F1 + 2. In conclusion, angiotensin II has mild platelet-activating effects in vivo and also enhances coagulation. Markers of platelet secretion are significantly increased, whereas markers of platelet aggregability are less affected. The clinical relevance of these findings remains to be clarified.

Solid-state Cross-Polarization Magic Angle Spinning Carbon-13 Nuclear Magnetic Resonance (CP/MAS 13C-NMR) has been used to investigate the structure and interactions of cellulose I. The use of spectral fitting for the extraction of information from CP/MAS 13C-NMR spectra is reviewed and results obtained are discussed. Examples are shown where the method has been used to monitor the structural changes occurring in wood cellulose during kraft pulping. The effects observed on the cellulose and hemicelluloses are further investigated using a model system. Assignments of signal intensities originating from xylan-cellulose interactions are made.

Risk factors for QTc interval prolongation and dispersion, indicators of an increased risk for cardiac arrhythmia and sudden death, have been investigated in patients with eating disorders (ED) and ongoing weight loss. Patients were characterized with regard to weight, body mass index (BMI; weight/length2), duration of weight loss, rate of weight loss and rate of weight loss immediately preceding examination. At examination, a 12-lead electrocardiographic (ECG) registration and blood samples for analysis of serum electrolytes were obtained. In total, 92 examinations in 58 female patients aged 15.5+/-1.7 (mean +/- SD) y were analysed. Control ECG recordings were obtained from 38 normal-weight teenage girls with no known heart disease. Patients with ED weighed 40.7+/-7.8 kg, corresponding to BMI 15.2+/-2.4 kg/m2 following a weight loss of 11.8+/-6.5 kg. In ED patients, the ECG showed bradycardia, a shift to the right of the QRS axis, diminished amplitudes of the QRS complex and T wave, and prolongation and increased dispersion of the QTc interval. In multiple regression analyses low weight, low BMI and rapid weight loss immediately preceding the examination were the most important independent predictors of QTc interval prolongation and dispersion. It is concluded that an ECG examination is an important part of the assessment of patients with ED and ongoing weight loss, even in the absence of electrolyte disturbances, and especially if the patient is severely underweight or weight loss is rapid.

Recent studies have suggested that angiotensin II may inhibit fibrinolysis. In order to further test this hypothesis, we investigated the acute effects of angiotensin II (intravenous infusion of 10 ng/kg per min over 15-20 min) on fibrinolytic function in 18 healthy men. Time-controls (n=11) and control experiments with a placebo infusion (n = 13) were also performed. The activities of plasmin activator inhibitor-1 (PAI-1) and tissue-type plasminogen activator (t-PA), as well as t-PA antigen levels, were determined in plasma before, during and 60 min after the infusion of angiotensin II. Angiotensin II caused a clear-cut elevation in blood pressure; heart rate and plasma noradrenaline levels tended to decrease during the infusion but increased afterwards, indicating reflexogenic adjustments. Plasma t-PA activity and antigen levels increased by 81+/-11 and 14+/-3%, respectively, during angiotensin II infusion (both P < 0.001), whereas t-PA activity was unchanged and t-PA antigen decreased (P < 0.05) in placebo experiments. PAI-1 activity decreased similarly in time-controls and during angiotensin infusion (P < 0.001). Thus, short-term infusion of angiotensin II enhances fibrinolysis by elevating plasma t-PA. It is not clear whether this is a direct angiotensin-receptor-mediated effect or if it is related to the hemodynamic effects of the infusion.

HIV-1 reverse transcriptase (RT) can specifically enhance HIV-1 proteinase activity in vitro and in eukaryotic cells (1). To determine if the effect of RT on proteinase activity was due to changes in the equilibrium dimerization constant of the proteinase or the stability of the proteinase dimer, we studied the effect of RT on a genetically engineered covalent dimer (tethered dimer) of the proteinase. RT was found to increase the activity of the tethered dimer independent of pH and ionic strength. The effect of RT on the kinetic constants (Km and kcat) of the wild type HIV-1 proteinase and its tethered dimer were also determined. These results show that RT can increase the enzymatic catalytic efficiency and substrate affinity of the proteinase, by a mechanism independent of promoting dimer formation.

Platelet function is dynamically regulated in vivo, and stress or exercise may have prothrombotic effects due to platelet activation. Platelets are intimately involved in primary hemostasis and it is possible that platelet activation may be a link between stress and myocardial infarction via several mechanisms--neuro-hormonal activation, increased shear stress, and an increased risk for plaque rupture with ensuing platelet activation. Catecholamines and stress may overcome the platelet inhibition afforded by aspirin, which may limit its efficacy in preventing myocardial infarction. Lipid lowering therapy would be expected to attenuate platelet activation, but results to the contrary are presented. New and more efficient platelet inhibitors may antagonize also stress induced platelet activation and be more efficient in the prevention of thrombotic complications, but their greater efficacy also entail a greater risk for bleeding complications.

Platelet function was studied in 10 patients with familial hypercholesterolaemia, following lipid-lowering treatment with selective LDL-apheresis and with the HMG-CoA reductase inhibitor pravastatin. Platelet function was assessed before, and 2, 5 and 14 days after LDL-apheresis, and before and after 4 weeks of pravastatin therapy. Both treatments significantly reduced total- and LDL-cholesterol, whereas LDL-apheresis also reduced VLDL-cholesterol. Lp(a)-levels were reduced by LDL-apheresis and elevated by pravastatin treatment. Pravastatin therapy significantly enhanced platelet aggregability in vivo, as measured by ex vivo filtragometry. Plasma serotonin levels also increased. Other markers of in vivo activation of platelets, i.e. beta-thromboglobulin in plasma and urine, and 11-dehydro-thromboxane B2 in urine were unaltered. Adenosine diphosphate-induced platelet aggregation in vitro remained unchanged during pravastatin therapy, and the platelet volume distribution was not affected. LDL-apheresis reduced the mean platelet volume, as well as the percentage of large platelets, whereas the percentage of small platelets increased. Other measures of platelet function in vivo or in vitro were, however, unaltered following LDL-apheresis. Thus, pravastatin therapy enhances certain aspects of platelet aggregability in vivo, whereas a single treatment with selective LDL-apheresis does not consistently affect platelet aggregability during resting conditions. These results do not support the concept that reduction of LDL-cholesterol improves platelet function in hypercholesterolaemic patients, at least not in the short-term. However, the reduction of platelet volume after LDL-apheresis may be beneficial for patients receiving this therapy regularly.

Background: Epinephrine and mental stress may, via platelet stimulation, enhance the risk of thrombus formation. Norepinephrine is more likely than epinephrine to activate platelets in vivo because of higher levels in plasma but is less well studied in this respect. The antiplatelet drug of choice for patients with coronary artery disease, aspirin, may be less effective during sympathoadrenal activation. We therefore investigated platelet responses in vivo to exogenous norepinephrine with and without aspirin pretreatment., Methods and Results: Platelet aggregability in vivo was assessed in 11 healthy male subjects, by filtragometry ex vivo (which reflects platelet aggregability in vivo) and by measurements of plasma beta-thromboglobulin (beta-TG, which reflects platelet secretion). Norepinephrine infusions elevated venous plasma norepinephrine from 1.5 to 4 and 15 nmol/L, respectively, and enhanced platelet aggregability (filtragometry) concentration dependently (P < .001). Platelet secretion (beta-TG levels) increased during high-dose infusion (P < .01). Aspirin pretreatment (500 mg orally 12 hours earlier) reduced the excretion of 11-dehydrothromboxane B2 by 62 +/- 5% (P < .001) and attenuated platelet aggregability at rest (P < .05) but not the effect of norepinephrine infusion on platelet aggregability. Conversely, resting plasma beta-TG levels and the urinary excretion of high-molecular-weight beta-TG were not altered by aspirin pretreatment, whereas the norepinephrine-induced increase in plasma beta-TG was abolished., Conclusions: Norepinephrine, at plasma levels easily attained during exercise, enhances platelet aggregability and platelet secretion in vivo in healthy humans. Aspirin may be less effective as an antithrombotic drug during sympathoadrenal activation in humans.

Serotonin (5-hydroxytryptamine, 5-HT) in blood is stored in platelets and has vascular and platelet stimulating effects when released into plasma. Accurate measurements of 5-HT in plasma are complicated by inadvertent platelet activation causing sampling artifacts and by analytical problems when determining trace levels. We developed an assay for plasma 5-HT based on solid-phase extraction (Sep-Pak C18), aqueous acetylation, pentafluoropropionylation, and negative ion chemical ionization gas chromatography-mass spectrometry. The method was able to recover 5-HT from plasma by > 90% and to quantitate with a precision of 7.5% at a level of 0.5 nmol/l. It was used to define blood sampling and sample handling procedures giving low and consistent values for 5-HT. A good blood sampling technique, adequate platelet stabilization in the test tube, and rapid high speed centrifugation of the blood resulted in low plasma levels of both 5-HT and beta-thromboglobulin (a platelet release product). Using these procedures plasma 5-HT levels in healthy volunteers were found to be 0.77 +/- 0.38 (mean +/- S.D.; range 0.27-1.49) nmol/l (n = 18), which is 4-100-fold lower than previously reported values.

1. A randomised double-blind placebo-controlled study was performed to investigate the effects of isosorbide dinitrate (ISDN; 20 mg orally) on various aspects of platelet function and fibrinolysis in vivo in 12 healthy volunteers. 2. Measurements were performed at rest (before and after tablet ingestion) and during platelet activation by adrenaline (0.4 nmol kg-1 min-1; 30 min infusion). 3. At rest, ISDN did not alter plasma concentrations of beta-thromboglobulin (beta TG). EC50 values for ADP induced aggregation in vitro (Born aggregometry) or ex vivo filtragometry readings. Adrenaline markedly increased platelet aggregability in vivo as measured by filtragometry and elevated levels of beta TG in plasma. ISDN treatment did not affect these responses in the group as a whole. 4. Individuals responding to ISDN with more pronounced vasodilatation at rest showed a lesser increase in aggregability during the ensuing adrenaline infusion (r = -0.66, P = 0.02) despite higher adrenaline levels during ISDN. In individuals showing a significant decrease in systolic blood pressure (n = 8) ISDN tended to attenuate the adrenaline induced increase in platelet aggregability (filtragometry; P = 0.08), despite higher plasma adrenaline and noradrenaline levels after ISDN ingestion. 5. Plasma concentrations of ISDN and its active metabolites isosorbide-5-mononitrate and isosorbide-2-mononitrate were not correlated to haemodynamic or platelet variables. 6. Fibrinolytic activity (t-PA antigen and activity, PAI-1 antigen and activity) increased similarly during the adrenaline infusion following ISDN and placebo. 7. It is concluded that ISDN may affect platelet aggregation responses to adrenaline in vivo, but only in individuals showing significant haemodynamic responses to ISDN.(ABSTRACT TRUNCATED AT 250 WORDS)