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2.
  • Butylina, Svetlana, et al. (författare)
  • Fractionation of whey-derived peptides using a combination of ultrafiltration and nanofiltration
  • 2006
  • Ingår i: Journal of Membrane Science. - : Elsevier. - 0376-7388 .- 1873-3123. ; 280:1-2, s. 418-426
  • Tidskriftsartikel (refereegranskat)abstract
    • This paper describes the fractionation and further isolation and characterisation of peptides and proteins present in sweet whey by means of ultrafiltration using a regenerated cellulose membrane with a nominal molar mass cut-off value of 10 kg/mol and nanofiltration through sulphonated polyether sulphone membrane with a cut-off of 1 kg/mol. The concentration of whey proteins was done below the critical flux. The sieving coefficients for the whey components (proteins, lactose and salts) were estimated. Whey proteins were completely rejected by the ultrafiltration membrane. Size exclusion chromatography (SEC) and matrix-assisted laser desorption ionisation time-of-flight (MALDI-TOF) mass spectrometry were used to evaluate the molar masses of the peptide fractions that were present in the whey permeates. Nanofiltration of whey permeates obtained after ultrafiltration was conducted at two pH values (9.5 and 3.0) that corresponded to the different charged states of the membrane and of the peptides. The transmission of peptides, amino acids and lactose was found to be mainly affected by the permeability of the fouling layer. The selectivity of the nanofiltration membranes toward peptides compared to lactose was calculated as 0.82 and 6.81 at pH 9.5 and 3.0, respectively.
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  • Butylina, Svetlana, et al. (författare)
  • Separation of nucleoprotein complexes with antioxidant activity from yeast Saccharomyces cerevisiae
  • 2007
  • Ingår i: Separation and Purification Technology. - : Elsevier BV. - 1383-5866 .- 1873-3794. ; 53:1, s. 64-70
  • Tidskriftsartikel (refereegranskat)abstract
    • In this study, complexes of nucleic acids and acidic nuclear proteins were isolated from baker's yeast cells of Saccharomyces cerevisiae by mild alkaline extraction followed by precipitation with acetic acid. The optimal composition of the buffer applied for extraction of nucleoprotein complexes was determined. The high and low molar mass fractions of the nucleoprotein complexes were separated using cross-flow microfiltration through track-etched membranes. The molar masses were determined by intrinsic viscosity measurements and the molar mass distribution in nucleoprotein complexes was studied by gel permeation chromatography. The protein component of the nucleoprotein complexes was purified on a strongly basic anion exchange resin. The high molar mass nucleoprotein complexes could induce the growth of culture cells of S. cerevisiae exposed to ultraviolet irradiation or treated with hydrogen peroxide
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  • Henricsson, Marianne, et al. (författare)
  • The incidence of retinopathy 10 years after diagnosis in young adult people with diabetes: results from the nationwide population-based Diabetes Incidence Study in Sweden (DISS).
  • 2003
  • Ingår i: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 26:2, s. 349-354
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE—To estimate the prevalence and severity of diabetic retinopathy (DR) 10 years after diagnosis in a nationwide population-based cohort study of young adult diabetic patients in Sweden. RESEARCH DESIGN AND METHODS—The Diabetes Incidence Study in Sweden (DISS) aims to register all incident cases of diabetes aged 15–34 years in Sweden. In 1987–1988, 806 cases were reported, and 627 (78%) of them were followed up with regard to retinopathy 8–10 years later. The assessment was based on retinal photographs in most cases (86%). RESULTS—Ten years after diagnosis, retinopathy was found in 247 patients (39%). The retinopathy was mild in 206 (33%), whereas 30 (4.8%) patients had moderate nonproliferative DR (NPDR) and 11 (1.8%) had proliferative DR (PDR). Patients with retinopathy had worse glycemic control during the years than patients without (HbA1c 8.1 ± 1.5% and 6.8 ± 1.2%, respectively; P < 0.001). In a Cox regression analysis, time to retinopathy was related to high HbA1c (P < 0.001) and high BMI (P = 0.001). Patients with type 2 diabetes had an increased prevalence of severe retinopathy (NPDR or PDR) compared with those with type 1 diabetes (14 of 93 [15%] versus no or mild 24 of 471 [5%], respectively; P < 0.001). CONCLUSIONS—Despite modern diabetes management, 39% of young adult diabetic patients developed retinopathy within the first 10 years of the disease. Nevertheless, compared with the prevalence of retinopathy (63%), after a similar duration of diabetes before the Diabetes Control and Complications Trial, this prevalence was clearly lower. Current treatment aimed to achieve strict glycemic control has reduced the risk for developing retinopathy.
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  • Kiritopoulos, Demostenis, et al. (författare)
  • Denosumab prevents acetabular bone loss around an uncemented cup : analysis of secondary outcomes in a randomized controlled trial
  • 2022
  • Ingår i: Acta Orthopaedica. - : Medical Journals Sweden AB. - 1745-3674 .- 1745-3682. ; 93, s. 709-720
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND AND PURPOSE: Uncemented total hip arthroplasty (THA) is associated with periprosthetic bone loss. In a secondary outcome analysis from a randomized controlled trial, we studied whether denosumab can prevent loss of acetabular periprosthetic bone mineral density (pBMD) in patients who received a trabecular metal cup during uncemented THA.PATIENTS AND METHODS: 64 patients (aged 35-65 years) with unilateral osteoarthritis of the hip were randomized to 2 subcutaneous injections with denosumab or placebo, given 1-3 days post-surgery and 6 months post-surgery. Acetabular pBMD was measured in 5 regions of interest (ROIs) by dual-energy X-ray absorptiometry. Serum markers for bone metabolism were analyzed. Periprosthetic osteoblastic activity, measured as standardized uptake values (SUVs) by [18F] positron emission tomography/computed tomography, was evaluated in 32 of the 64 study patients.RESULTS: After 12 months, patients treated with denosumab had higher pBMD compared with the placebo-treated patients in 4 of 5 ROIs and in sum of ROIs 1-5. After 24 months, the effect on pBMD for patients treated with denosumab declined. Serum markers declined pronouncedly up to 12 months in patients treated with denosumab, but rebounded above baseline levels after 24 months. Patients treated with denosumab had statistically significantly lower SUVs in all ROIs, except ROI 5, after 6 months.INTERPRETATION: Based on this exploratory analysis of secondary endpoints the application of denosumab seems associated with preserved acetabular pBMD, reduced bone metabolism and attenuated periprosthetic osteoblastic activity. However, given the known rebound affects after discontinuation of denosumab treatment, these effects cannot be expected to persist. If prolonged treatment or shift to other regimes would be beneficial to reduce the risk of cup loosening is yet to be investigated.
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8.
  • Kraft, Jamie D., et al. (författare)
  • Lipoxins modulate neutrophil oxidative burst, integrin expression and lymphatic transmigration differentially in human health and atherosclerosis
  • 2022
  • Ingår i: FASEB Journal. - Hoboken, NJ, United States : John Wiley & Sons. - 0892-6638 .- 1530-6860. ; 36:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Dysregulated chronic inflammation plays a crucial role in the pathophysiology of atherosclerosis and may be a result of impaired resolution. Thus, restoring levels of specialized pro-resolving mediators (SPMs) to promote the resolution of inflammation has been proposed as a therapeutic strategy for patients with atherosclerosis, in addition to standard clinical care. Herein, we evaluated the effects of the SPM lipids, lipoxin A4 (LXA4) and lipoxin B4 (LXB4), on neutrophils isolated from patients with atherosclerosis compared with healthy controls. Patients displayed altered endogenous SPM production, and we demonstrated that lipoxin treatment in whole blood from atherosclerosis patients attenuates neutrophil oxidative burst, a key contributor to atherosclerotic development. We found the opposite effect in neutrophils from healthy controls, indicating a potential mechanism whereby lipoxins aid the endogenous neutrophil function in health but reduce its excessive activation in disease. We also demonstrated that lipoxins attenuated upregulation of the high-affinity conformation of the CD11b/CD18 integrin, which plays a central role in clot activation and atherosclerosis. Finally, LXB4 enhanced lymphatic transmigration of human neutrophils isolated from patients with atherosclerosis. This finding is noteworthy, as impaired lymphatic function is now recognized as an important contributor to atherosclerosis. Although both lipoxins modulated neutrophil function, LXB4 displayed more potent effects than LXA4 in humans. This study highlights the therapeutic potential of lipoxins in atherosclerotic disease and demonstrates that the effect of these SPMs may be specifically tailored to the need of the individual. © 2022 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.
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  • Niehorster, Diederick C, et al. (författare)
  • Behavioral science labs : How to solve the multi-user problem
  • Ingår i: Behavior Research Methods. - 1554-3528.
  • Tidskriftsartikel (refereegranskat)abstract
    • When lab resources are shared among multiple research projects, issues such as experimental integrity, replicability, and data safety become important. Different research projects often need different software and settings that may well conflict with one another, and data collected for one project may not be safeguarded from exposure to researchers from other projects. In this paper we provide an infrastructure design and an open-source tool, labManager, that render multi-user lab facilities in the behavioral sciences accessible to research projects with widely varying needs. The solutions proposed ensure ease of management while simultaneously offering maximum flexibility by providing research projects with fully separated bare metal environments. This solution also ensures that collected data is kept separate, and compliant with relevant ethical standards and regulations such as General Data Protection Regulation (GDPR) legislation. Furthermore, we discuss preconditions for running shared lab facilities and provide practical advice.
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  • Nyström, Andreas, et al. (författare)
  • Denosumab Prevents Early Periprosthetic Bone Loss After Uncemented Total Hip Arthroplasty : Results from a Randomized Placebo-Controlled Clinical Trial
  • 2020
  • Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431 .- 1523-4681. ; 35:2, s. 239-247
  • Tidskriftsartikel (refereegranskat)abstract
    • Implant loosening is the most common indication for revision surgery after total hip arthroplasty (THA). Although bone resorption around the implants plays a pivotal role in the pathophysiology of loosening, it is unknown whether potent early inhibition of osteoclasts could mitigate this process and thus reduce the need for revision surgery. We performed a randomized, double-blind, placebo-controlled phase 2 trial in 64 patients aged 35 to 65 years with unilateral osteoarthritis of the hip. They underwent surgery with an uncemented THA and were randomized to either two subcutaneous doses of denosumab (n = 32) or placebo (n = 32) given 1 to 3 days and 6 months after surgery. Patients were followed for 24 months. Primary outcome was periprosthetic bone mineral density (BMD) of the hip at 12 months as measured by dual-energy X-ray absorptiometry (DXA). In addition, [18 F] sodium fluoride positron emission tomography/CT (F-PET) was performed in half of the patients for analysis of periprosthetic standardized uptake value (SUV). Analyses were made according to intention-to-treat principles. The trial was registered at ClinicalTrials.gov 2011-001481-18, NCT01630941. Denosumab potently inhibited early periprosthetic bone loss. After 12 months, BMD in the denosumab group was 32% (95% confidence interval [CI] 22-44) higher in Gruen zone 7 and 11% (95% CI 8-15) higher in zones 1 to 7. After 24 months, the difference in BMD between groups had decreased to 15% (95% CI 4-27) in zone 7 and 4% (95% CI 0-8) in zones 1 to 7. In both groups, SUV increased after surgery, but the increase was less pronounced in the denosumab group. Biochemical markers of bone metabolism decreased in the denosumab group in the first 12 months, but a rebound effect with marker concentrations above baseline was observed after 24 months. Denosumab potently prevents early periprosthetic bone loss after uncemented THA; however, the effect diminishes after discontinuation of treatment. Further research is needed to determine whether this bone loss will prove to be of clinical importance and, if so, whether the positive effect observed in this study could be preserved by either prolonged treatment with denosumab or additional antiresorptive treatment.
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  • Nyström, Marianne, et al. (författare)
  • NF retention and critical flux of small hydrophilic/hydrophobic molecules
  • 2004
  • Ingår i: Membrane Technology. - 0958-2118 .- 1873-4049. ; 10, s. 5-8
  • Tidskriftsartikel (refereegranskat)abstract
    • This feature article provides details of a study in which small molar mass substances were used as model substances in nanofiltration using NF-270 and Desal-5 DL membranes. The hydrophobicities of the substances were calculated, and flux, retention and critical flux were measured for the filtration and related to flow conditions and characteristics of model compounds and membranes.
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15.
  • Platt, Samantha, et al. (författare)
  • Retention of pegs in cross-flow ultrafiltration through membranes
  • 2002
  • Ingår i: Desalination. - 0011-9164 .- 1873-4464. ; 149:1-3, s. 417-422
  • Tidskriftsartikel (refereegranskat)abstract
    • This work investigated the difference between membrane cut-offs measured with the CHARMME methods and the values quoted from the manufacturers. Four different membranes were characterised. The two regenerated cellulose membranes that according to the manufacturers had cut-offs of 5 and 10 kD had, in fact, the same cut-off of 2.5 kD. It was also found that the polyethersulfone membrane had a lower cut-off (3 kD) than that stated by the membrane manufacturers (5 kD). A cross-flow velocity of 2 m/s and a flux of 40 1/h/m2 was found to keep the mass transfer coefficient within a tolerable range for all PEGs used.
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  • Svanberg, Cecilia, 1991- (författare)
  • HIV-1 Exploitation of Dendritic Cell Functionality and Initial Responses in Mucosal Tissues : Elucidation of Influence of HIV-1 Complement Opsonization, and HIV-1-HSV-2 Co-infection
  • 2023
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Human immunodeficiency virus (HIV)-1 is transmitted between individuals via sexual intercourse or via blood products. To date there are 38 million people living with chronic HIV infection and around 1.5 million yearly acquire a new infection. HIV is known to have detrimental effects on the immune system and its cell function and leads to the development of acquired immune deficiency syndrome (AIDS). AIDS is characterized by opportunistic infections often fatal to the individual. Mucosal tissues, which are the main site of HIV-1 infection, consist of a complex network of different cell types building up a barrier against the outside world. In the mucosa there are multiple immune cells and one of them is the dendritic cells (DCs), a professional antigen presenting cell needed for priming of adaptive T cell responses. DCs are rarely productively infected with HIV-1 but the virus can modulate the DC phenotype and function by mere exposure to the virus. There are many factors that influence viral transmission including prevalent inflammatory conditions or infections in the genital tract. For instance, a newly acquired herpes simplex virus-2 (HSV-2) infection increases the risk of transmission at HIV-1 exposure by four times. A vital part of the innate immune defense is the complement system, which consists of proteins found in all body fluids. Normally during complement activation, it leads to lysis of pathogens, but HIV-1 can evade this process. This is achieved by the incorporated complement regulatory proteins in the viral plasma membrane leading to accumulation of opsonizing complement fragments on the HIV-1 particles. Our aim with these studies was to deepen the understanding of the HIV-1 exploitation of DC function and elucidate the initial effects exposure and establishment of HIV-1 infection has on the mucosal tissues and immune cells. In addition, we aimed to elucidate the effects HSV-2 exerts on the HIV-1-infection of DCs and how viral complement opsonization affects the viral infection and activation of immune responses. In Paper I we found that coinfection of monocyte derived DCs (MDDCs) with HIV-1 and HSV-2 decreases the amount of the HIV-1 restriction factors SAMHD1 and TREX1 in MDDCs, leading to increased productive HIV-1 infection. In Paper II and III we found that HIV-1 utilizes the complement system to induce higher productive infection of the colorectal and cervical mucosal DCs. The different forms of HIV, free or complement opsonized, had distinct effects on the immune responses and T cell phenotypes in the tissues, all in favor of HIV-1 establishment and productive infection. In Paper IV, HIV-1 exposed DCs triggered after crosstalk with suppressive T cells a prolonged type I interferon response and an upregulation of coinhibitory molecules on the DCs. The findings in this thesis add to the knowledge of HIV-1 early transmission events, how co-infection modulates DC function, and how the presence of HIV-1 affects the priming of adaptive immune responses. 
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17.
  • Svensson, K. E., et al. (författare)
  • Effects of mother-infant skin-to-skin contact on severe latch-on problems in older infants : A randomized trial
  • 2013
  • Ingår i: International Breastfeeding Journal. - : Springer Science and Business Media LLC. - 1746-4358. ; 8:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Infants with latch-on problems cause stress for parents and staff, often resulting in early termination of breastfeeding. Healthy newborns experiencing skin-to-skin contact at birth are pre-programmed to find the mother's breast. This study investigates if skin-to-skin contact between mothers with older infants having severe latching on problems would resolve the problem.Methods: Mother-infant pairs with severe latch-on problems, that were not resolved during screening procedures at two maternity hospitals in Stockholm 1998-2004, were randomly assigned to skin-to-skin contact (experimental group) or not (control group) during breastfeeding. Breastfeeding counseling was given to both groups according to a standard model. Participants were unaware of their treatment group. Objectives were to compare treatment groups concerning the proportion of infants regularly latching on, the time from intervention to regular latching on and maternal emotions and pain before and during breastfeeding.Results: On hundred and three mother-infant pairs with severe latch-on problems 1-16 weeks postpartum were randomly assigned and analyzed. There was no significant difference between the groups in the proportion of infants starting regular latching-on (75% experimental group, vs. 86% control group). Experimental group infants, who latched on, had a significantly shorter median time from start of intervention to regular latching on than control infants, 2.0 weeks (Q1 = 1.0, Q3 = 3.7) vs. 4.7 weeks (Q1 = 2.0, Q3 = 8.0), (p-value = 0.020). However, more infants in the experimental group (94%), with a history of " strong reaction" during " hands-on latch intervention" , latched-on within 3 weeks compared to 33% in the control infants (Fisher Exact test p-value = 0.0001). Mothers in the experimental group (n = 53) had a more positive breastfeeding experience according to the Breastfeeding Emotional Scale during the intervention than mothers in the control group (n = 50) (p-value = 0.022).Conclusions: Skin-to-skin contact during breastfeeding seems to immediately enhance maternal positive feelings and shorten the time it takes to resolve severe latch-on problems in the infants who started to latch. An underlying mechanism may be that skin-to-skin contact with the mother during breastfeeding may calm infants with earlier strong reaction to " hands on latch intervention" and relieve the stress which may have blocked the infant's inborn biological program to find the breast and latch on.Trial registration: Karolinska Clinical Trial Registration number CT20100055.
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  • Svensson, Maria, et al. (författare)
  • Signs of nephropathy may occur early in young adults with diabetes despite modern diabetes management : Results from the nationwide population-based Diabetes Incidence Study in Sweden (DISS)
  • 2003
  • Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 26:10, s. 2903-2909
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE - To estimate the occurrence of early-onset renal involvement in a nationwide population-based cohort of young adults with diabetes in Sweden and relate the findings to glycemic control, type of diabetes, sex, smoking, and blood pressure. RESEARCH DESIGN AND METHODS - The Diabetes Incidence Study in Sweden aims to register all incident cases of diabetes in the age-group 15-34 years. In 1987-1988, 806 patients were reported and invited to participate in a follow-up study focusing on microvascular complications. Of them, 469 subjects participated. The assessment was based on questionnaires (n = 469), blood samples (n = 424), urine samples (n = 251) and, when appropriate, medical records (n = 186). RESULTS - During the follow-up time, median 9 years (range 6-12), 31 of 469 patients (6.6%) with incipient or overt diabetic nephropathy (i.e., micro- or macroalbuminuria) were found, 24 of 426 (5.6%) in type 1 and 7 of 43 (16%) in type 2 diabetic subjects (P = 0.016). Additionally, 24 of 31 patients (77%) had microalbuminuria and 7 (23%) had macroalbuminuria, which mainly occurred in patients with type 2 diabetes. In a Cox regression analysis, high mean HbA1c during the follow-up period and high blood pressure at follow-up increased the risk of developing signs of nephropathy (P = 0.020 and P = 0.003, respectively). Compared with patients with type 1 diabetes, those with type 2 diabetes tended to have an increased risk of renal involvement (P = 0.054) when adjusting for sex, tobacco use, glycemic control, and blood pressure. CONCLUSIONS - Despite modern treatment and self-monitoring of blood glucose, young adult patients with diabetes may still develop renal involvement during the first 10 years of diabetes duration. Inadequate HbA 1c high blood pressure, and type 2 diabetes appear to be risk markers for early occurrence of diabetic nephropathy.
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  • Waldenström, Jesper, 1985, et al. (författare)
  • Absence of interferon-lambda 4 enhances spontaneous clearance of acute hepatitis C virus genotypes 1-3 infection
  • 2021
  • Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 56:7
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives Absence of a functional interferon-lambda 4 (IFN-lambda 4) gene (IFNL4) predicts spontaneous resolution of acute hepatitis C virus (HCV) infections in regions with a predominance of genotype 1, whereas variants of the inosine triphosphate pyrophosphatase (ITPase) gene (ITPA) entailing reduced activity associate with increased sustained virologic response rates following some therapeutic regimens. This study aimed at investigating the impact of IFNL4 on acute HCV genotype 2 or 3 infections, and whether ITPase activity influenced outcome. Materials and Methods Two hundred and seven people who injected drugs (PWID) with documented anti-HCV seroconversion, and 57 PWID with reinfection with HCV were analyzed regarding IFNL4 (rs368234815 and rs12979860) and ITPA (rs1127354 and rs7270101), and longitudinally followed regarding HCV RNA. Results The spontaneous clearance of HCV infection in anti-HCV seronegative PWID was enhanced when IFN-lambda 4 was absent (44% vs. 20% for IFNL4 TT/TTrs1368234815 and Delta G(rs1368234815) respectively, p < .001; OR 3.2) across genotypes 1-3. The proportion lacking IFN-lambda 4 was further increased following resolution of repeated re-exposure to HCV (74% among re-infected participants who had cleared at least two documented HCV infections). ITPA genetic variants did not independently impact on the outcome, but among males lacking IFN-lambda 4, reduced ITPase activity markedly augmented the likelihood of resolution (65% vs. 29% for <100% and 100% ITPase activity, p = .006). Conclusions Absence of IFN-lambda 4 entails an enhanced likelihood of spontaneous resolution both following primary acute infection and repeated re-exposure to HCV across genotypes 1-3. Among men lacking IFN-lambda 4, reduced ITPase activity improved outcome.
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