Publications by authors named "Liisa Virkki"

28 Publications

  • Page 1 of 1

Lactose- and cellobiose-derived branched trisaccharides and a sucrose-containing trisaccharide produced by acceptor reactions of Weissella confusa dextransucrase.

Food Chem 2016 Jan 19;190:226-236. Epub 2015 May 19.

Department of Food and Environmental Sciences, P.O. Box 27, FI-00014 University of Helsinki, Finland.

Dextran-producing Weissella have received significant attention. However, except for maltose, the acceptor reactions of Weissella dextransucrases with different sugars have not been investigated. The action of recombinant Weissella confusa VTT E-90392 dextransucrase was tested with several potential acceptors, particularly, analogs lactose and cellobiose. The major acceptor products of both disaccharides were identified as branched trisaccharides, with a glucosyl residue α-(1 → 2)-linked to the acceptor's reducing end. An additional product, isomelezitose (6(Fru)-α-Glcp-sucrose), was also produced when using lactose as an acceptor. This is the first report of the synthesis of isomelezitose by a dextransucrase. The NMR spectra of the three trisaccharides were fully assigned, and their structures were confirmed by selective enzymatic hydrolysis. The trisaccharides prepared from (13)C6(glc) sucrose and lactose were analyzed by ESI-MS(n), and the fragmentation patterns of these compounds were characterized.
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http://dx.doi.org/10.1016/j.foodchem.2015.05.090DOI Listing
January 2016

The impact of fermentation with exopolysaccharide producing lactic acid bacteria on rheological, chemical and sensory properties of pureed carrots (Daucus carota L.).

Int J Food Microbiol 2015 Aug 23;207:109-18. Epub 2015 Apr 23.

VTT Technical Research Centre of Finland Ltd, P.O. Box 1000, FI-02044 VTT Espoo, Finland.

Fermentation with lactic acid bacteria (LAB) offers a natural means to modify technological and nutritional properties of foods and food ingredients. This study explored the impact of fermentation with different exopolysaccharide (EPS) producing LAB on rheological, chemical and sensory properties of puréed carrots in water, as a vegetable model, with the focus on texture formation. The screening of 37 LAB strains for starter selection revealed 16 Lactobacillus, Leuconostoc and Weissella strains capable of EPS (dextran, levan, and/or β-glucan) production in the carrot raw material. Fermentations with five out of six selected EPS producers modified perceived texture of the liquid carrot model (p<0.05). The formation of low-branched dextran correlated with perceived thickness, whereas the production of β-glucan correlated with perceived elasticity. Low-branched dextran producing Weissella confusa and Leuconostoc lactis strains produced thick texture accompanied by pleasant odour and flavour. The fermentation with the selected EPS-producing LAB strains is a promising clean label approach to replace hydrocolloid additives as texturizers in vegetable containing products, not only carrot.
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http://dx.doi.org/10.1016/j.ijfoodmicro.2015.04.031DOI Listing
August 2015

Rates of serious infections and malignancies among patients with rheumatoid arthritis receiving either tumor necrosis factor inhibitor or rituximab therapy.

J Rheumatol 2015 Mar 15;42(3):372-8. Epub 2015 Jan 15.

From the University of Helsinki, and the Helsinki University Central Hospital, Helsinki; Jyväskylä Central Hospital, Jyväskylä; Tampere University Hospital, Tampere; Turku University Central Hospital, Turku; South Karelia Central Hospital, Lappeenranta; Kanta-Häme Central Hospital, Hämeenlinna, Finland.K.J. Aaltonen, MSc (pharm); J.T. Joensuu, MSc (pharm); L. Virkki, MSc (pharm); P. Aronen, MSc; M. Blom, PhD, Professor, University of Helsinki; T. Sokka, MD, PhD, Adj. Professor, Jyväskylä Central Hospital; H. Relas, MD, PhD; H. Valleala, MD, PhD, Adj. Professor, Helsinki University Central Hospital; V. Rantalaiho, MD, PhD, Tampere University Hospital; L. Pirilä, MD, PhD, Turku University Central Hospital; K. Puolakka, MD, PhD, Adj. Professor, South Karelia Central Hospital; T. Uusitalo, MD, Kanta-Häme Central Hospital; Y.T. Konttinen, MD, PhD, Professor; D. Nordström, MD, PhD, Adj. Professor, University of Helsinki, and the Helsinki University Central Hospital.

Objective: Because of the role of tumor necrosis factor (TNF) in host defense, it was hypothesized that its inhibition might lead to an increased risk of malignancies and infections. The objective of our study was to assess the incidence of serious infections leading to hospitalization and malignancies among patients with rheumatoid arthritis (RA) receiving either TNF inhibitor or rituximab (RTX) therapy.

Methods: The study population was identified from the National Register for Biologic Treatment in Finland and the hospital records of Central Finland Central Hospital for conventional disease-modifying antirheumatic drug (cDMARD) users. Data on infections and malignancies were acquired from national healthcare registers. A Poisson model was used to calculate the adjusted incidence rate ratios (aIRR) and was composed of age, sex, time from diagnosis, year of the beginning of the followup, rheumatoid factor status, Disease Activity Score at 28 joints, Health Assessment Questionnaire, prior malignancy, prior serious infection, prior biologic use, and time-updated use of methotrexate, sulfasalazine, hydroxychloroquine, and oral corticosteroids as confounders.

Results: In total, during the followup of 10,994 patient-years, 92 malignancies and 341 serious infections were included in the analyses. The aIRR of infections compared to cDMARD users were 1.2 (95% CI 0.63-2.3), 0.84 (95% CI 0.53-1.3), 0.98 (95% CI 0.60-1.6), and 1.1 (95% CI 0.59-1.9) for the patients treated with infliximab (IFX), etanercept, adalimumab, and RTX, respectively. The crude rates of malignancies were highest among the users of cDMARD and RTX, and lowest among patients treated with IFX with no differences in aIRR.

Conclusion: Our results provide some reassurance of the safety of biologic treatments in the treatment of RA.
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http://dx.doi.org/10.3899/jrheum.140853DOI Listing
March 2015

O-acetylation of glucuronoxylan in Arabidopsis thaliana wild type and its change in xylan biosynthesis mutants.

Glycobiology 2014 Jun 17;24(6):494-506. Epub 2014 Mar 17.

Department of Food and Environmental Sciences, Faculty of Agriculture and Forestry, University of Helsinki, PO Box 27, 00014, Finland.

O-Acetylglucuronoxylans (AcGX) in Arabidopsis thaliana carry acetyl residues on the 2-O and/or 3-O positions of the xylopyranosyl (Xylp) units, but the distribution of different O-acetylated Xylp units is partly unclear. We studied a possible correlation of xylan acetylation and the activities of different glycosyltransferases involved in xylan biosynthesis by analyzing the distribution of O-acetyl substituents on AcGX from Arabidopsis wild-type and mutants irx7, irx9-1, irx10, irx14 and gux1gux2. The relative contents of the Xylp structural units were determined with quantitative two-dimensional heteronuclear single quantum coherence nuclear magnetic resonance spectroscopy. In the wild type, the degree of acetylation (DA) was 60%. Mono- and diacetylated Xylp units constituted 44 and 6% of the AcGX backbone, respectively; while (4-O-methyl)-glucopyranosyluronic acid (1 → 2)-linked Xylp units, most of which also carry 3-O-acetylation, represented 13%. The DA was decreased in irx7, irx9-1 and irx14 due to the decrease in monoacetylation (2-O and 3-O), indicating a relationship between acetylation and other AcGX biosynthetic processes. The possible interactions that could lead to such changes have been discussed. No change in DA was observed in irx10 and gux1gux2, but monoacetylation was nonetheless elevated in gux1gux2. This indicates that acetylation occurs after addition of GlcpA to the xylan backbone. Mass fragmentation analysis suggests that the prevalent acetylation pattern is the acetyl group added on every other Xylp unit.
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http://dx.doi.org/10.1093/glycob/cwu017DOI Listing
June 2014

Challenges in analysis of high-molar mass dextrans: comparison of HPSEC, AsFlFFF and DOSY NMR spectroscopy.

Carbohydr Polym 2014 Jan 21;99:199-207. Epub 2013 Aug 21.

Department of Food and Environmental Sciences, P.O. Box 27, FIN-00014 University of Helsinki, Finland. Electronic address:

Dilute solutions of various dextran standards, a high-molar mass (HMM) commercial dextran from Leuconostoc spp., and HMM dextrans isolated from Weissella confusa and Leuconostoc citreum were analyzed with high-performance size-exclusion chromatography (HPSEC), asymmetric flow field-flow fractionation (AsFlFFF), and diffusion-ordered NMR spectroscopy (DOSY). HPSEC analyses were performed in aqueous and dimethyl sulfoxide (DMSO) solutions, while only aqueous solutions were utilized in AsFlFFF and DOSY. The study showed that all methods were applicable to dextran analysis, but differences between the aqueous and DMSO-based solutions were obtained for HMM samples. These differences were attributed to the presence of aggregates in aqueous solution that were less prevalent in DMSO. The study showed that DOSY provides an estimate of the size of HMM dextrans, though calibration standards may be required for each experimental set-up. To our knowledge, this is the first study utilizing these three methods in analyzing HMM dextrans.
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http://dx.doi.org/10.1016/j.carbpol.2013.08.021DOI Listing
January 2014

Do biologic drugs affect the need for and outcome of joint replacements in patients with rheumatoid arthritis? A register-based study.

Semin Arthritis Rheum 2013 Aug 5;43(1):55-62. Epub 2013 Mar 5.

Faculty of Pharmacy, Division of Social Pharmacy, University of Helsinki, Helsinki, Finland.

Objectives: The aim was to study the incidence of joint replacements among biologic drug and disease-modifying anti-rheumatic drug (DMARD) users as well as to investigate the plausible effect of biologic treatment on survival of prostheses in patients with Rheumatoid arthritis (RA).

Methods: The study population comprised 2 cohorts of patients [Register of biologic treatment in Finland (ROB-FIN) and the Central Finland RA database] from 1999 to 2010. Records of joint replacements performed in the study population between 1980 and 2010 were retrieved from the Finnish Arthroplasty Register. Propensity score matching was used to equalize patient characteristics between biologics and DMARD users. The incidence rates of primary and revision operations were compared between the 2 treatment groups. Kaplan-Meier survival analysis was used to analyze prosthesis survival.

Results: Of the 2102 biologics and 2710 DMARD users identified from the registries, 1587 were included in both groups after the matching. Median follow-up times were 3.1 and 8.0 years, respectively. There were more primary operations per 100 patient years in the biologics (3.89, CI 95% 3.41-4.41) vs. DMARD (2.63, 2.35-2.94) group but slightly fewer revisions (0.65, 0.46-0.88 vs. 0.83, 0.68-1.01). Biologics users were more likely to receive a joint replacement to small joints (p < 0.001). The survival of the prostheses installed during or prior to follow-up was similar in both treatment groups.

Conclusions: The use of biologic drugs did not reduce the need for joint replacement surgery in patients with a similar on-medication disease activity. Despite possibly lower rate of revisions among biologic users, the durability of prostheses was not improved.
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http://dx.doi.org/10.1016/j.semarthrit.2013.01.002DOI Listing
August 2013

Structural analysis of linear mixed-linkage glucooligosaccharides by tandem mass spectrometry.

Food Chem 2013 Feb 2;136(3-4):1496-507. Epub 2012 Oct 2.

Department of Food and Environmental Sciences, P.O. Box 27, FIN-00014 University of Helsinki, Finland.

Dextrans and glucooligosaccharides (GLOS) are produced by lactic acid bacteria (LAB) during sourdough fermentation. The dextrans can act as hydrocolloids in sourdough bread, while the GLOS may have antistaling and prebiotic properties, depending on their structure. Development of high-throughput methods for screening the structural properties of dextrans and GLOS produced by different LAB in varying fermentation conditions is therefore of interest. In this study we explored the possibility of using electrospray ionisation tandem mass spectroscopy (ESI-MS/MS) to unequivocally determine the structures of underivatised GLOS. The emphasis was on linear mixed linked model GLOS, especially those containing (1→3) linkages that are common in dextrans. After evaluation of the model GLOS, the ESI-MS/MS method was used to determine the linkage positions of two mixed-linked tetrasaccharides obtained by hydrolysis of Weissella confusa and Leuconostoc citreum dextrans. In positive mode, only the reducing end linkage could be determined because isomeric fragment ions, present in subsequent MS(n) cycles, hindered assignment of the remaining linkages. By contrast, it was possible to unambiguously assign all the linkages in each GLOS using the negative mode spectra. The present study thus shows that negative mode is the preferred method for ESI-MS/MS structural analysis of underivatised GLOS. In combination with liquid chromatography this method will enable rapid profiling of the structural variation of dextrans and prebiotic GLOS.
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http://dx.doi.org/10.1016/j.foodchem.2012.09.075DOI Listing
February 2013

Quantitation of 4-O-methylglucuronic acid from plant cell walls.

Carbohydr Polym 2013 Jan 30;91(2):626-30. Epub 2012 Aug 30.

Department of Food and Environmental Sciences, Faculty of Agriculture and Forestry, P.O. Box 27, FI-00014 University of Helsinki, Helsinki, Finland.

The accuracy of commercial α-D-glucopyranosyl uronic acid (GlcA) as a calibration standard for the determination of the 4-O-methyl-α-D-glucopyranosyl uronic acid (meGlcA) content in plant materials was studied. A batch of meGlcA standard was purified from commercial birch xylan and quantified using nuclear magnetic resonance spectroscopy. Both commercial GlcA and the purified meGlcA were used as standards for the quantitation of meGlcA in Arabidopsis thaliana stems, as well as wood and wheat straw samples using acid methanolysis and gas chromatography (GC). The GlcA standard was partially lactonized during acid methanolysis, thus yielding six glycoside peaks in GC. If all six GlcA-derived peaks were included in the GlcA calibration curve, the calculated meGlcA content was underestimated by 30% compared with that obtained using the purified meGlcA as a standard. The meGlcA content was best estimated by including either the two main GlcA peaks or only peaks corresponding to pyranosides and furanosides of GlcA in the calibration curve.
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http://dx.doi.org/10.1016/j.carbpol.2012.08.078DOI Listing
January 2013

Role and regulation of VEGF and its receptors 1 and 2 in the aseptic loosening of total hip implants.

J Orthop Res 2012 Nov 23;30(11):1830-6. Epub 2012 Apr 23.

Mikkeli Central Hospital, 50100 Mikkeli, Finland.

It was hypothesized that vascular endothelial growth factor (VEGF) in fibroblasts participates in aseptic loosening of total hip replacement (THR) implants. Therefore, osteoarthritic (OA) samples (n = 11) were compared with synovial membrane-like interface tissues from revision THR (n = 10). VEGF-A and its receptors were stained using streptavidin-immunoperoxidase method. Their regulation by hypoxia and cytokines were studied in cultured fibroblasts using quantitative real-time polymerase chain reaction (qRT-PCR). VEGFR1(+) lining cells (p < 0.01), stromal fibroblast-like cells (p = 0.001) and stromal macrophage-like cells (p < 0.05) were more numerous in rTHR than in OA. As to VEGFR2(+), only stromal fibroblast-like cells in rTHR outnumbered those found in OA (p < 0.05). VEGFRs in synovial fibroblasts were not affected by hypoxia, but VEGF increased 2.4-fold (p < 0.05). Interleukin-4 up-regulated VEGFR1 expression 23-fold. This is the first study to describe a difference between rTHR and OA in VEGF receptors, particularly VEGFR1. Hypoxia increased VEGF, but the VEGFR1 increase in the lining and stroma is probably IL-4 driven, in accordance with the M2-type macrophage dominance in interface tissues. VEGF/VEGFR system is also affected by hypoxia and may play a role in angiogenesis and bone pathology in aseptic loosening of total hip implants.
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http://dx.doi.org/10.1002/jor.22138DOI Listing
November 2012

Substituent-specific antibody against glucuronoxylan reveals close association of glucuronic acid and acetyl substituents and distinct labeling patterns in tree species.

Planta 2012 Aug 24;236(2):739-51. Epub 2012 Apr 24.

Department of Food and Environmental Sciences, University of Helsinki, PO Box 27, 00014, Helsinki, Finland.

Immunolabeling can be used to locate plant cell wall carbohydrates or other components to specific cell types or to specific regions of the wall. Some antibodies against xylans exist; however, many partly react with the xylan backbone and thus provide limited information on the type of substituents present in various xylans. We have produced a monoclonal antibody which specifically recognizes glucopyranosyl uronic acid (GlcA), or its 4-O-methyl ether (meGlcA), substituents in xylan and has no cross-reactivity with linear or arabinofuranosyl-substituted xylans. The UX1 antibody binds most strongly to (me)GlcA substitutions at the non-reducing ends of xylan chains, but has a low cross-reactivity with internal substitutions as well, at least on oligosaccharides. The antibody labeled plant cell walls from both mono- and dicotyledons, but in most tissues an alkaline pretreatment was needed for antibody binding. The treatment removed acetyl groups from xylan, indicating that the vicinity of glucuronic acid substituents is also acetylated. The novel labeling patterns observed in the xylem of tree species suggested that differences within the cell wall exist both in acetylation degree and in glucuronic acid content.
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http://dx.doi.org/10.1007/s00425-012-1653-7DOI Listing
August 2012

Systematic review and meta-analysis of the efficacy and safety of existing TNF blocking agents in treatment of rheumatoid arthritis.

PLoS One 2012 17;7(1):e30275. Epub 2012 Jan 17.

Faculty of Pharmacy, University of Helsinki, Helsinki, Finland.

Background And Objectives: Five-tumour necrosis factor (TNF)-blockers (infliximab, etanercept, adalimumab, certolizumab pegol and golimumab) are available for treatment of rheumatoid arthritis. Only few clinical trials compare one TNF-blocker to another. Hence, a systematic review is required to indirectly compare the substances. The aim of our study is to estimate the efficacy and the safety of TNF-blockers in the treatment of rheumatoid arthritis (RA) and indirectly compare all five currently available blockers by combining the results from included randomized clinical trials (RCT).

Methods: A systematic literature review was conducted using databases including: MEDLINE, SCOPUS (including EMBASE), Cochrane library and electronic search alerts. Only articles reporting double-blind RCTs of TNF-blockers vs. placebo, with or without concomitant methotrexate (MTX), in treatment of RA were selected. Data collected were information of patients, interventions, controls, outcomes, study methods and eventual sources of bias.

Results: Forty-one articles reporting on 26 RCTs were included in the systematic review and meta-analysis. Five RCTs studied infliximab, seven etanercept, eight adalimumab, three golimumab and three certolizumab. TNF-blockers were more efficacious than placebo at all time points but were comparable to MTX. TNF-blocker and MTX combination was superior to either MTX or TNF-blocker alone. Increasing doses did not improve the efficacy. TNF-blockers were relatively safe compared to either MTX or placebo.

Conclusions: No single substance clearly rose above others in efficacy, but the results of the safety analyses suggest that etanercept might be the safest alternative. Interestingly, MTX performs nearly identically considering both efficacy and safety aspects with a margin of costs.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0030275PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3260264PMC
June 2012

Molecular characterization and solution properties of enzymatically tailored arabinoxylans.

Int J Biol Macromol 2011 Dec 26;49(5):963-9. Epub 2011 Aug 26.

Department of Food and Environmental Sciences, PO Box 27, FIN-00014 University of Helsinki, Finland.

Two α-L-arabinofuranosidases with different substrate specificities were used to modify the arabinose-to-xylose ratio of cereal arabinoxylans: one enzyme (AXH-m) removed the L-arabinofuranosyl substituents from the monosubstituted xylopyranosyl residues and the other (AXH-d3) the (1→3)-linked L-arabinofuranosyl units from the disubstituted xylopyranosyl residue. In this study, we noticed that not only the arabinose-to-xylose ratio but also the position of the arabinofuranosyl substituents affects the water-solubility of arabinoxylans. The AXH-d3 treatment had no significant effect on the solution conformation of arabinoxylans, but the density of the arabinoxylan molecules decreased in DMSO solution after AXH-m modification. The possible heterogeneity of arabinoxylans complicated the interpretation of data describing the macromolecular properties of the enzymatically modified samples.
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http://dx.doi.org/10.1016/j.ijbiomac.2011.08.020DOI Listing
December 2011

Outcomes of switching anti-TNF drugs in rheumatoid arthritis--a study based on observational data from the Finnish Register of Biological Treatment (ROB-FIN).

Clin Rheumatol 2011 Nov 7;30(11):1447-54. Epub 2011 Jun 7.

University of Helsinki, Haartmaninkatu 8, Helsinki, Finland.

The aim of this study was to assess, based on observational data from the Finnish Register of Biological Treatment, the outcomes of switching an initial tumor necrosis factor (TNF) blocker to another in the treatment of rheumatoid arthritis (RA). RA patients, who started biological therapy with a TNF blocker between May 1999 and April 2009 and who switched to another TNF blocker, were studied (n=479). The outcomes were assessed according to the reason for and type of the switch. Outcome assessments included American College of Rheumatology 50 responder index (ACR50) response at 3 months after the switch, treatment duration of the second TNF blocker, and swollen joint counts, CRP and DAS28 score at the 3 months, best and last observations of the first and second TNF blocker, respectively. In those who switched due to lack of effectiveness (LOE), the disease activity parameters fell significantly from baseline upon use of infliximab or adalimumab, but had increased prior to the switch. Switching to another TNF blocker (etanercept or adalimumab) restored the response initially achieved with the first TNF blocker. The disease activity parameters fell significantly from baseline upon use of etanercept, and were maintained but not further improved after switching to adalimumab. TNF blocker switching seemed to be most beneficial in secondary LOE (defined as loss of ACR50 response). In those who switched due to adverse events (AE) or other reasons, a similar degree of response as had been achieved with the first agent was also achieved and maintained with the second agent. The results suggest that a second TNF blocker can restore the response in cases of secondary LOE and maintain it after switching due to an AE.
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http://dx.doi.org/10.1007/s10067-011-1779-1DOI Listing
November 2011

Structural analysis of enzyme-resistant isomaltooligosaccharides reveals the elongation of α-(1→3)-linked branches in Weissella confusa dextran.

Biomacromolecules 2011 Feb 5;12(2):409-18. Epub 2011 Jan 5.

Department of Food and Environmental Sciences, University of Helsinki, Helsinki, Finland.

Weissella confusa VTT E-90392 is an efficient producer of a dextran that is mainly composed of α-(1→6)-linked D-glucosyl units and very few α-(1→3) branch linkages. A mixture of the Chaetomium erraticum endodextranase and the Aspergillus niger α-glucosidase was used to hydrolyze W. confusa dextran to glucose and a set of enzyme-resistant isomaltooligosaccharides. Two of the oligosaccharides (tetra- and hexasaccharide) were isolated in pure form and their structures elucidated. The tetrasaccharide had a nonreducing end terminal α-(1→3)-linked glucosyl unit (α-D-Glcp-(1→3)-α-D-Glcp-(1→6)-α-D-Glcp-(1→6)-α-D-Glc), whereas the hexasaccharide had an α-(1→3)-linked isomaltosyl side group (α-D-Glcp-(1→6)[α-D-Glcp-(1→6)-α-D-Glcp-(1→3)]-α-D-Glcp-(1→6)-α-D-Glcp-(1→6)-α-D-Glc). A mixture of two isomeric oligosaccharides was also obtained in the pentasaccharide fraction, which were identified as (α-D-Glcp-(1→6)-α-D-Glcp-(1→3)-α-D-Glcp-(1→6)-α-D-Glcp-(1→6)-α-D-Glc) and (α-D-Glcp-(1→6)[α-D-Glcp-(1→3)]-α-D-Glcp-(1→6)-α-D-Glcp-(1→6)-α-D-Glc). The structures of the oligosaccharides indicated that W. confusa dextran contains both terminal and elongated α-(1→3)-branches. This is the first report evidencing the presence of elongated branches in W. confusa dextran. The (1)H and (13)C NMR spectroscopic data on the enzyme-resistant isomaltooligosaccharides with α-(1→3)-linked glucosyl and isomaltosyl groups are published here for the first time.
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http://dx.doi.org/10.1021/bm1011536DOI Listing
February 2011

Biological therapy for psoriatic arthritis in clinical practice: outcomes up to 2 years.

J Rheumatol 2010 Nov 17;37(11):2362-8. Epub 2010 Aug 17.

University of Helsinki, Finland.

Objective: To evaluate the performance of biological drugs in psoriatic arthritis (PsA) in a routine care setting, using the Finnish national register of biological treatment (ROB-FIN).

Methods: Patients with PsA who started therapy with infliximab or etanercept between June 2000 and February 2006 (n = 127) were followed for up to 24 months. Response was evaluated using American College of Rheumatology response criteria including individual measures.

Results: Significantly diminished values for swollen and tender joints, patient's global and pain assessments, doctor's global assessment of disease activity, erythrocyte sedimentation rate, C-reactive protein, and Health Assessment Questionnaire score were observed within 3 months after commencement of both infliximab and etanercept. Values remained significantly lower throughout the 24 months of followup. ACR20 response at 3 months was 79% (n = 22/28) for infliximab and 76% (n = 34/45) for etanercept. The first biological drug was discontinued in 16% due to lack of effectiveness and in 6% due to adverse events.

Conclusion: Anti-tumor necrosis factor-α therapy, often combined with conventional disease-modifying antirheumatic drugs, appeared to have limited toxicity and persistent effectiveness for up to 2 years in a cohort of Finnish patients with severe peripheral PsA.
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http://dx.doi.org/10.3899/jrheum.091477DOI Listing
November 2010

[Biological therapy in rheumatoid arthritis based on ten years of registry surveillance in Finland].

Duodecim 2010 ;126(12):1487-95

HYKS:n yleissisätautien ja reumatologian klinikka, PL 340, 00029 HUS.

Biological drugs are used in the treatment of active inflammatory athritides refractory to conventional treatment. Data from the Finnish registry of biological treatment (ROB-FIN) indicates that the effectiveness of the biologicals in clinical practice corresponds to or even excels that of randomized controlled clinical trials, and seems to endure in patients continuing treatment. About one-fifth of rheumatoid arthritis patients discontinue treatment due to lack of effectiveness, and one-tenth due to adverse events. Serious adverse events were seen in 2.5% of all patients. In the future electronic follow-up, pharmacogenetics, and biomarker research may help to better optimize treatment individually.
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August 2010

Dehydroepiandrosterone (DHEA) substitution treatment for severe fatigue in DHEA-deficient patients with primary Sjögren's syndrome.

Arthritis Care Res (Hoboken) 2010 Jan;62(1):118-24

Helsinki University Central Hospital, Helsinki, Finland.

Objective: Primary Sjögren's syndrome (SS) is characterized by fatigue and low levels of serum dehydroepiandrosterone/dehydroepiandrosterone sulfate (DHEA/DHEAS). Our aim was to study whether SS patients with severe fatigue and low serum DHEAS values benefit from DHEA substitution (50 mg/day).

Methods: A multicenter, investigator-based, powered, randomized controlled clinical trial (crossover, washout design) using fatigue as the primary outcome measure was performed on patients with primary SS (n = 107) who had a general fatigue score > or =14 on the 20-item Multiple Fatigue Inventory (MFI-20), combined with age- and sex-adjusted serum DHEAS values below the mean. Fatigue was assessed using MFI-20 subscales, i.e., general fatigue, physical fatigue, mental fatigue, reduced motivation, and activity (scale 4-20), and with a visual analog scale (VAS; scale 0-100).

Results: In an intent-to-treat analysis, a 50-mg DHEA substitution dose and placebo similarly improved fatigue. All of the MFI-20 subscales and the fatigue VAS improved from the baseline levels as a result of treatment (P < 0.001), but with negligible differences between these 2 treatments. The mean between-treatment difference was -0.1 for general fatigue (the primary outcome measure), 0.0 for physical fatigue, 0.0 for mental fatigue, 0.0 for reduced motivation, 0.3 for reduced activity, and 2.2 for the fatigue VAS. None of these differences was statistically significant.

Conclusion: Similar to earlier results using pharmacologic doses, substitution treatment with 50 mg of DHEA in DHEA-deficient and severely tired primary SS patients does not help against fatigue better than placebo. This may relate to the prohormone nature of DHEA and its recently described defective intracrine tissue-specific conversion to active sex steroids in SS.
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http://dx.doi.org/10.1002/acr.20022DOI Listing
January 2010

Presence of 1-->3-linked 2-O-beta-d-xylopyranosyl-alpha-l-arabinofuranosyl side chains in cereal arabinoxylans.

Carbohydr Res 2009 Dec 2;344(18):2480-8. Epub 2009 Oct 2.

Department of Applied Chemistry and Microbiology, Faculty of Agriculture and Forestry, University of Helsinki, Finland.

The presence of a fairly uncommon side chain 2-O-beta-D-xylopyranosyl-alpha-L-arabinofuranosyl in arabinoxylans (AX) from eight different cereal by-products was investigated, using (1)H NMR spectroscopy and high-performance anion-exchange chromatography with pulsed amperometric detection (HPAEC-PAD) after Shearzyme (GH10 endo-1,4-beta-D-xylanase) hydrolysis. This disaccharide side group was present in significant amounts in AX extracted from corn cobs and barley husks. For the first time, it was also detected in AX from oat spelts and rice husks, and in lesser amounts in wheat straw AX. Arabinoxylo-oligosaccharide (AXOS) containing the 2-O-beta-D-Xylp-alpha-L-Araf side chain was purified from the oat spelt AX hydrolysate and the structure was fully analyzed using 1D and 2D NMR spectroscopy. The AXOS was identified as beta-D-Xylp-(1-->2)-alpha-L-Araf-(1-->3)-beta-D-Xylp-(1-->4)-D-Xyl. To our knowledge, such a structure with 2-O-beta-D-Xylp-alpha-L-Araf attached to the O-3 of the nonreducing end of xylobiose has not been described previously. New information on substitution of AX from various cereal by-products was obtained by combining NMR and enzyme-assisted HPAEC-PAD analysis.
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http://dx.doi.org/10.1016/j.carres.2009.09.035DOI Listing
December 2009

In situ production and analysis of Weissella confusa dextran in wheat sourdough.

Food Microbiol 2009 Oct 17;26(7):734-43. Epub 2009 Jul 17.

VTT Technical Research Centre of Finland, Espoo, Finland.

Several lactic acid bacteria belonging to the genera Leuconostoc, Lactobacillus, and Weissella have been introduced to wheat sourdough baking for in situ production of exopolysaccharides. This is considered a novel method for improving the shelf-life, volume and nutritional value of bread without additives. However, in situ production of exopolysaccharides during sourdough fermentation is challenged by simultaneous acidification due to metabolic activities of the bacteria, which may significantly diminish the positive technological impact of exopolysaccharides. In this study, the growth, activity and in situ production of dextran by Weissella confusa VTT E-90392 in wheat sourdoughs were investigated. Furthermore, the influence of dextran-enriched sourdoughs, at the addition level of 43%, on the subsequent bread quality was established. W. confusa efficiently produced dextran from the added sucrose in wheat sourdough without strong acid production. A new specific enzyme-assisted method for in situ analysis of dextran in sourdoughs was developed. With this method, we could for the first time proof significant (11-16 g/kg DW) production of polymeric dextran in sourdoughs. Concomitant formation of shorter isomaltooligosaccharides by W. confusa was also detected. The produced dextran significantly increased the viscosity of the sourdoughs. Application of dextran-enriched sourdoughs in bread baking provided mildly acidic wheat bread with improved volume (up to 10%) and crumb softness (25-40%) during 6 days of storage. Hence, W. confusa is a promising new strain for efficient in situ production of dextrans and isomaltooligosaccharides in sourdoughs without strong acidification.
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http://dx.doi.org/10.1016/j.fm.2009.07.008DOI Listing
October 2009

Comprehensive multidetector HPSEC study on solution properties of cereal arabinoxylans in aqueous and DMSO solutions.

Biomacromolecules 2009 Jul 5;10(7):1962-9. Epub 2009 Jun 5.

Department of Applied Chemistry and Microbiology, P.O. Box 27, FIN-00014 University of Helsinki, Finland.

The water-soluble arabinoxylans from wheat flour (high, medium, and low viscosity samples) and rye flour (high viscosity sample) were characterized by (1)H NMR spectroscopy and HPSEC with refractive index, light scattering, and viscometric detectors. These cereal arabinoxylans have recently been used as model arabinoxylans in various studies, but their solution properties have not been previously investigated. In this study, two HPSEC eluent systems were used: the water-based system and DMSO-based system. DMSO seemed to be a better solvent than water, especially for arabinoxylans containing a low amount of arabinose substituents. (1)H NMR spectroscopy indicated the structural differences between the analyzed arabinoxylan samples that also affected the hydrodynamic parameters obtained with HPSEC. Influence of arabinose side groups on the solution conformation of arabinoxylans could not be excluded based on our data, despite the role of arabinose substituents being questioned in previous investigations concerning arabinoxylan conformation in solution.
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http://dx.doi.org/10.1021/bm9003767DOI Listing
July 2009

Step-wise enzymatic preparation and structural characterization of singly and doubly substituted arabinoxylo-oligosaccharides with non-reducing end terminal branches.

Carbohydr Res 2008 Dec 24;343(18):3049-57. Epub 2008 Sep 24.

Department of Applied Chemistry and Microbiology, Faculty of Agriculture and Forestry, University of Helsinki, Finland.

Shearzyme (GH10 endo-1,4-beta-D-xylanase) and two different alpha-L-arabinofuranosidases (AXH-m and AXH-d3) were used stepwise to manufacture arabinoxylo-oligosaccharides (AXOS) with alpha-L-Araf (1-->2)-monosubstituted beta-D-Xylp residues or alpha-L-Araf (1-->2)- and (1-->3) doubly substituted beta-D-Xylp residues from wheat arabinoxylan (AX) in a rather straightforward way. Four major AXOS (d-I, d-II, m-I and m-II) were formed in two separate hydrolyses. The AXOS were purified and the structures were confirmed using TLC, HPAEC-PAD, MALDI-TOF-MS and 1D and 2D NMR spectroscopy. The samples were identified as d-I: alpha-L-Araf-(1-->2)-[alpha-L-Araf-(1-->3)]-beta-D-Xylp-(1-->4)-beta-D-Xylp-(1-->4)-D-Xylp, d-II: alpha-L-Araf-(1-->2)-[alpha-L-Araf-(1-->3)]-beta-D-Xylp-(1-->4)-D-Xylp, m-I: alpha-L-Araf-(1-->2)-beta-D-Xylp-(1-->4)-beta-D-Xylp-(1-->4)-D-Xylp and m-II: alpha-L-Araf-(1-->2)-beta-D-Xylp-(1-->4)-D-Xylp. To our knowledge, this is the first report on structural (1)H and (13)C NMR analysis of xylobiose-derived AXOS d-II and m-II. The latter compound has not been reported previously. The doubly substituted AXOS were produced for the first time in good yields, as d-I and d-II corresponded to 11.8 and 5.6 wt% of AX, respectively. Singly alpha-L-Araf (1-->2)-substituted AXOS could also be prepared in similar yields by treating the doubly substituted AXOS further with AXH-d3.
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http://dx.doi.org/10.1016/j.carres.2008.09.013DOI Listing
December 2008

Androgen deficiency and defective intracrine processing of dehydroepiandrosterone in salivary glands in Sjögren's syndrome.

J Rheumatol 2008 Nov 1;35(11):2229-35. Epub 2008 Oct 1.

Institute of Clinical Medicine, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland.

Objective: .We hypothesized that in addition to dehydroepiandrosterone (DHEA) depletion, Sjögren's syndrome (SS) is characterized by local androgen deficiency in salivary glands and defects in local processing of DHEA.

Methods: Sex steroid levels in serum and saliva were measured using enzyme immunoassays. Androgen effects on salivary gland cells were analyzed using the cysteine-rich secretory protein-3 (CRISP-3) androgen biomarker.

Results: Serum and salivary concentrations of androgens were low in SS. Substrate to end-product ratios and correlations suggest that in SS salivary glands DHEA is effectively converted to testosterone, but that there are defects in converting testosterone further to dihydrotestosterone (DHT). In healthy controls no such phenomenon was seen, but testosterone is effectively converted to DHT. Salivary glands contained type I 5-alpha-reductase, and its inhibition with dutasteride completely blocked the upregulating effect of DHEA, but not of DHT, on CRISP-3 in human salivary gland acinar cells.

Conclusion: DHEA and DHT upregulate CRISP-3, which is reportedly low in SS. The effect of DHEA on CRISP-3 is indirect and is inhibited by dutasteride, showing that there is intracrine processing of DHEA in salivary glands. In healthy glands, but not in SS, DHEA is effectively taken up and converted to DHT. Sex steroid concentrations in saliva in part reflect glandular uptake of DHEA-sulfate and local intracrine DHEA metabolism, which seem to be defective in SS. Our study demonstrates a prominent androgen deficiency and a defect in intracrine production of active androgens in SS salivary glands, also suggesting that salivary DHT cannot be maintained at a normal level in this female-dominant autoimmune exocrinopathy.
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http://dx.doi.org/10.3899/jrheum.080220DOI Listing
November 2008

New operative technique for treatment of arthroscopically-confirmed injury to the scapholunate ligament by volar capsuloplasty augmented with a free tendon graft.

Scand J Plast Reconstr Surg Hand Surg 2008 ;42(5):260-6

Orto-Laakarit Medical Center, Helsinki, Finland.

We report how scapholunate (SL) lesions found during arthroscopy were treated using a new palmar operation based on the use of a tendon loop formed using the palmaris longus tendon, with promising preliminary results. Scapholunate instability induced by hyperextension injury was diagnosed and graded arthroscopically. Volar capsuloplasty was then done by free tendon graft in the same session in 31 patients with grades II-IV scapholunate instability. Half of the patients operated on had a normal range of movement, and all except one had flexion-extension of at least 75% of the normal. Half of the patients had no pain or limitations of the use of the wrist, and although half the patients had some pain on exertion, not one had severe pain. These results are comparable to, or even better than, those reported using other methods of repair. The combined procedure saves money, diminishes the total recuperation time and, as autologous tissues are used for the repair, secondary operations for removal of the implant are unnecessary. This method seems to be a useful adjunct to the types of operative treatment available, although it is apparently not suitable in static grade IV SL instability.
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http://dx.doi.org/10.1080/02844310802210822DOI Listing
January 2009

Structural comparison of arabinoxylans from two barley side-stream fractions.

J Agric Food Chem 2008 Jul 13;56(13):5069-77. Epub 2008 Jun 13.

Department of Applied Chemistry and Microbiology, P.O. Box 27, FIN-00014, University of Helsinki, Finland.

The structures of barley ( Hordeum vulgare) arabinoxylans isolated from two industrial side fractions, barley husks (BH) and barley fiber (BF), were characterized. Arabinoxylans were extracted with saturated barium hydroxide after enzymatic pretreatment. Barium hydroxide was selective toward arabinoxylans, and only a minor amount of glucose-containing material was coextracted. Acid methanolysis followed by gas chromatography, 1H NMR spectroscopy, and specific enzymatic treatments followed by anion exchange chromatography with pulse amperometric detection (HPAEC-PAD) revealed that the chemical structure of barley husk arabinoxylan (BHAX) clearly differed from that of barley fiber arabinoxylan (BFAX). BFAX was more branched, containing more beta-D-xylopyranosyl (beta-D-Xylp) residues carrying alpha-L-arabinofuranosyl (alpha-L-Araf) units at both O-2 and O-3 positions. BHAX, on the other hand, contained more 2-O-beta-D-Xyl p-alpha-L-Ara f substituents than BFAX. BHAX and BFAX also differed with respect to the hydrodynamic properties investigated with multidetector size exclusion chromatography. BFAX had a higher weight-average molar mass and larger hydrodynamic volume, the latter indicating less dense conformation than BHAX. Mn, Mw /Mn, Rh, and the Mark-Houwink a value were also determined for both arabinoxylans.
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http://dx.doi.org/10.1021/jf800315qDOI Listing
July 2008

NMR spectroscopic analysis of exopolysaccharides produced by Leuconostoc citreum and Weissella confusa.

Carbohydr Res 2008 Jul 13;343(9):1446-55. Epub 2008 Apr 13.

Department of Applied Chemistry and Microbiology, Faculty of Agriculture and Forestry, University of Helsinki, PO Box 27, FIN-00014 Helsinki, Finland.

Dextrans are the main exopolysaccharides produced by Leuconostoc species. Other dextran-producing lactic acid bacteria include Streptococci, Lactobacilli, and Weissella species. Commercial production and structural analysis has focused mainly on dextrans from Leuconostoc species, particularly on Leuconostoc mesenteroides strains. In this study, we used NMR spectroscopy techniques to analyze the structures of dextrans produced by Leuconostoc citreum E497 and Weissella confusa E392. The dextrans were compared to that of L. mesenteroides B512F produced under the same conditions. Generally, W. confusa E392 showed better growth and produced more EPS than did L. citreum E497 and L. mesenteroides B512F. Both L. citreum E497 and W. confusa E392 produced a class 1 dextran. Dextran from L. citreum E497 contained about 11% alpha-(1-->2) and about 3.5% alpha-(1-->3)-linked branches whereas dextran from W. confusa E392 was linear with only a few (2.7%) alpha-(1-->3)-linked branches. Dextran from W. confusa E392 was found to be more linear than that of L. mesenteroides B512F, which, according to the present study, contained about 4.1% alpha-(1-->3)-linked branches. Functionality, whether physiological or technological, depends on the structure of the polysaccharide. Dextran from L. citreum E497 may be useful as a source of prebiotic gluco-oligosaccharides with alpha-(1-->2)-linked branches, whereas W. confusa E392 could be a suitable alternative to widely used L. mesenteroides B512F in the production of linear dextran.
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http://dx.doi.org/10.1016/j.carres.2008.04.012DOI Listing
July 2008

New enzyme-based method for analysis of water-soluble wheat arabinoxylans.

Carbohydr Res 2008 Feb 4;343(3):521-9. Epub 2007 Nov 4.

Department of Applied Chemistry and Microbiology, Faculty of Agriculture and Forestry, PO Box 27, FIN-00014 University of Helsinki, Finland.

Arabinoxylans (AX) are the predominant cell-wall polysaccharides in wheat flour. Water-extractable AX are essential for dough and bread properties and performance. However, there is no specific and accurate way of determining the content and structure of AX. An enzyme-assisted method employing an efficient enzyme mixture for the total hydrolysis of AX was developed in the present work. Enzymatic hydrolysis (EH) is a gentle method during which no unwanted sugar destruction occurs. Following EH, liberated monosaccharides were analysed by gas chromatography (GC) and liquid chromatography using HPAEC-PAD. The results were compared with acid methanolysis (AM) and acid hydrolysis (AH). EH performed better on commercially isolated AX samples than the reference method AM. Its action in the water extract from wheat flour was also more efficient than that of AM and comparable to the efficiency of AH. HPAEC-PAD revealed a significant amount of fructose in the water extract following EH, originating from fructans in wheat flour not detected in the GC analysis. The wheat flour examined contained 0.29% water-extractable AX. The arabinose/xylose ratio was 0.32. The enzyme-based method developed is applicable for comparison of different wheat flours and can be used in evaluating the effect of processing on the content and structure of water-extractable AX.
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http://dx.doi.org/10.1016/j.carres.2007.10.029DOI Listing
February 2008

Correction of chronic lunotriquetral instability using extensor retinacular split: a retrospective study of 26 patients.

Acta Orthop Belg 2007 Aug;73(4):451-7

Orto-Lääkärit Medical Center Helsinki, Finland.

Arthroscopy offers a welcome and reliable supplement to the current tool set for the diagnosis of lunotriquetral (LT) instability. This study reports the findings of LT-lesions during arthroscopy and the clinical results obtained after using dorsal stabilisation in its surgical management using extensor retinacular split. LT-instability of grade I-III was diagnosed in 26 patients. Imaging results were normal, Reagan's ballottement and Watson tests were positive in 47% and 79%, respectively. After arthroscopic diagnosis, the procedure was immediately continued with an open repair utilising an 8-10 mm wide and radial-based extensor retinacular split for dorsal capsular reinforcement. At 39 months (range: 14 to 84) follow-up, 64% had no or only occasional mild pain and 36% had pain with overuse or lifting. Overall scoring encompassing pain, patient satisfaction, range of motion and grip strength, was excellent in 24% and good in 64%. Only three patients had fair results, one after a further injury leading to distal radio-ulnar joint (DRUJ) instability, and two with concurrent DRUJ-stabilisation. One further patient required a secondary procedure. Arthroscopy seems to allow accurate diagnosis of LT-instability and can be continued in the same session using a straightforward reconstruction procedure providing satisfactory results.
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August 2007

The influence of sex steroids on Sjögren's syndrome.

Ann N Y Acad Sci 2007 Jun;1108:426-32

Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland.

Sjögren's syndrome is an autoimmune disease affecting the exocrine glands, most typically salivary and lacrimal glands. In Sjögren's syndrome, the acinar cells of these glands are damaged and destroyed, leading to diminished secretion of saliva and tear fluid. Accordingly, the current American-European criteria of Sjögren's syndrome include xerostomia (dry mouth) and keratoconjunctivitis sicca (dry eyes). In addition to these sicca symptoms and signs, the diagnostic criteria require autoimmune features in the form of Sjögren's syndrome SS-A and/or SS-B autoantibodies and lymphocyte infiltrates in labial salivary glands. Majority of patients with Sjögren's syndrome are women and the diagnosis is usually done when they are 40-50 years old. The cause of Sjögren's syndrome is unknown, but taking into account the female dominance and the late onset, our hypothesis is that sex steroids play a key role in the etiology of Sjögren's syndrome. More specifically, we believe that the driving factor behind Sjögren's syndrome could be lack of androgens. It has been shown that patients with Sjögren's syndrome have low concentrations of circulating dehydroepiandrosterone sulfate (DHEA-S) compared to age-matched healthy controls. Our hypothesis is that patients with Sjögren's syndrome suffer from an insufficient local androgen effect in the exocrine target tissues of the disease because of low systemic levels and/or ineffective local intracrine handling of DHEA-S prohormone. To further clarify the role of sex steroids and the eventual deficiency of androgens, salivary glands are studied using protein markers regulated by androgens or estrogens.
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http://dx.doi.org/10.1196/annals.1422.045DOI Listing
June 2007
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