| 1. |
- Barauskas, Justas, et al.
(author)
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''Sponge" nanoparticle dispersions in aqueous mixtures of diglycerol monooleate, glycerol dioleate, and polysorbate 80
- 2006
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In: Langmuir. - : American Chemical Society (ACS). - 0743-7463 .- 1520-5827. ; 22:14, s. 6328-6334
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Journal article (peer-reviewed)abstract
- Lipid nanoparticles of nonlamellar lyotropic phases have a wide solubilizing and encapsulating spectrum for a range of substances thanks to their nanostructured interior featuring both lipophilic and hydrophilic domains. As a consequence, these systems have emerged as promising drug delivery systems in various pharmaceutical and diagnostic applications. Here we present the phase behavior and dispersion properties of a novel three-component lipid system composed of diglycerol monooleate (DGMO), glycerol dioleate (GDO), and polysorbate 80 (P80) which shows several advantageous features relating to drug delivery applications including: spontaneous dispersion formation with a narrow size distribution and tunable particle phase-structure. The obtained phase diagram shows the presence of lamellar (L-alpha), hexagonal (H-2), and reverse bicontinuous cubic (V-2) liquid crystalline phases and an inverse micellar (L-2) solution. A particularly interesting observation is the presence of a phase region where two liquid phases coexist, most likely the L-2 and L-3 ("sponge phase"). These two phase structures appear also to coexist in the submicron particles formed in the dilute water region, where the L-3 element appears to stabilize nanoparticles with inner L-2 structure. Increasing the fraction of the dispersing P80 component results in the growth of the more water rich L-3 "surface phase" at the expense of the size of the inner L-2 core.
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| 2. |
- de la Vega, Maria Pagnon, et al.
(author)
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The Uppsala APP deletion causes early onset autosomal dominant Alzheimer's disease by altering APP processing and increasing amyloid beta fibril formation
- 2021
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In: Science Translational Medicine. - : American Association for the Advancement of Science (AAAS). - 1946-6234 .- 1946-6242. ; 13:606
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Journal article (peer-reviewed)abstract
- Point mutations in the amyloid precursor protein gene (APP) cause familial Alzheimer's disease (AD) by increasing generation or altering conformation of amyloid beta (A beta). Here, we describe the Uppsala APP mutation (Delta 690-695), the first reported deletion causing autosomal dominant AD. Affected individuals have an age at symptom onset in their early forties and suffer from a rapidly progressing disease course. Symptoms and biomarkers are typical of AD, with the exception of normal cerebrospinal fluid (CSF) A beta 42 and only slightly pathological amyloid-positron emission tomography signals. Mass spectrometry and Western blot analyses of patient CSF and media from experimental cell cultures indicate that the Uppsala APP mutation alters APP processing by increasing beta-secretase cleavage and affecting alpha-secretase cleavage. Furthermore, in vitro aggregation studies and analyses of patient brain tissue samples indicate that the longer form of mutated A beta, A beta Upp1-42(Delta 19-24), accelerates the formation of fibrils with unique polymorphs and their deposition into amyloid plaques in the affected brain.
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| 3. |
- Dominguez, Cecilia A., et al.
(author)
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The DQB1*03:02 HLA haplotype is associated with increased risk of chronic pain after inguinal hernia surgery and lumbar disc herniation
- 2013
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In: Pain. - : Ovid Technologies (Wolters Kluwer Health). - 0304-3959 .- 1872-6623. ; 154:3, s. 427-433
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Journal article (peer-reviewed)abstract
- Neuropathic pain conditions are common after nerve injuries and are suggested to be regulated in part by genetic factors. We have previously demonstrated a strong genetic influence of the rat major histocompatibility complex on development of neuropathic pain behavior after peripheral nerve injury. In order to study if the corresponding human leukocyte antigen complex (HLA) also influences susceptibility to pain, we performed an association study in patients that had undergone surgery for inguinal hernia (n = 189). One group had developed a chronic pain state following the surgical procedure, while the control group had undergone the same type of operation, without any persistent pain. HLA DRB1genotyping revealed a significantly increased proportion of patients in the pain group carrying DRB1*04 compared to patients in the pain-free group. Additional typing of the DQB1 gene further strengthened the association; carriers of the DQB1*03:02 allele together with DRB1*04 displayed an increased risk of postsurgery pain with an odds risk of 3.16 (1.61-6.22) compared to noncarriers. This finding was subsequently replicated in the clinical material of patients with lumbar disc herniation (n = 258), where carriers of the DQB1*03:02 allele displayed a slower recovery and increased pain. In conclusion, we here for the first time demonstrate that there is an HLA-dependent risk of developing pain after surgery or lumbar disc herniation; mediated by the DRB1*04 - DQB1*03:02 haplotype. Further experimental and clinical studies are needed to fine-map the HLA effect and to address underlying mechanisms.
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| 4. |
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| 5. |
- Gunnarsson, Torsten, 1945-, et al.
(author)
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Carl Larsson
- 2008
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Book (other academic/artistic)
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| 6. |
- Gunnarsson, Torsten, 1945-
(author)
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Carl Larsson
- 2007
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Book (other academic/artistic)
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| 7. |
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| 8. |
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| 9. |
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| 10. |
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| 11. |
- Gunnarsson, Torsten, et al.
(author)
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Recycling of fecal pellets in isopods : Microorganisms and nitrogen compounds as potential food for Oniscus asellus L
- 1986
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In: Soil Biology and Biochemistry. - : Elsevier BV. - 0038-0717. ; 18:6, s. 595-600
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Journal article (peer-reviewed)abstract
- The isopod Oniscus asellus was fed wood pieces. The fecal pellets produced during 6 days were reingested twice. Both fresh and ageing pellets were examined for microorganisms and nitrogen compounds including proteins and bacterial cell wall compounds, d-alanine and diaminopimelic acid. In old pellets, the plate counts of fungi decreased but that of bacteria as well as the concentrations of proteins and bacterial cell wall compounds increased from the first to the third gut passage. Immediately after a gut passage, the counts of microorganisms were lower than before the passage whereas the concentrations of bacterial cell wall compounds and proteins were higher. This indicates that both growth and lysis of bacteria occurred in the guts but that a considerable part of the bacterial cells were not digested and assimilated by the isopods. Comparison of the bacterial cell wall compounds also indicated shifts in the ratio of Gram-positive and Gram-negative bacteria during gut passages and during ageing of the fecal pellets. The concentration of total N did not markedly change after the second and third gut passages, indicating that the availability of N decreased due to accumulation of N into relatively recalcitrant proteins and bacterial cell walls.
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| 12. |
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| 13. |
- Hedlund, K., et al.
(author)
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Mate choice and male competition in Orchesella cincta (Collembola)
- 1990
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In: Experientia. - 0014-4754. ; 46:5, s. 524-526
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Journal article (peer-reviewed)abstract
- Both male and female Orchesella cincta (Collembola) were able to discriminate between spermatophores of different origin. Females chose spermatophores deposited by closely related males while males preferentially destroyed spermatophores of other males.
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| 14. |
- Kalliomäki, Maija-L, et al.
(author)
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Long-term pain after inguinal hernia repair in a population-based cohort; risk factors and interference with daily activities
- 2008
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In: European Journal of Pain. - : Wiley. - 1090-3801 .- 1532-2149. ; 12:2, s. 214-225
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Journal article (peer-reviewed)abstract
- In the Swedish Hernia Register 2834 inguinal hernia repairs in 2583 patients were registered in the county of Uppsala 1998-2004. In May 2005 the 2421 patients still alive were requested by mail to fill in a validated questionnaire concerning postherniorrhaphy pain. The final response rate became 72%. Altogether 519 patients (29%) stated that they had pain in the operated groin to some extent during past week. In 98 patients (6%) the pain interfered with daily activities. Factors associated with an increased risk of residual pain in a multivariate logistic regression analysis were age below median, operation for recurrence, open repair technique, history of preoperative pain, and less than three years from surgery. Factors not associated with occurrence of residual pain were gender, method of anaesthesia during surgery, hernia sac diameter, postoperative complications, hernia type, need for emergency operation, reducibility of the hernia sac and complete dissection of the hernia sac. Factors found to be associated with impairment of function due to pain in a multivariate logistic regression analysis were: age below median, female gender, medial hernia, open repair technique, postoperative complications, need for operation for recurrence, presence of preoperative pain and less than three years from surgery. The possibility of long-term pain as an outcome after hernia operations should be taken into consideration in the decision making prior to operation.
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| 15. |
- Kalliomäki, Maija-L, et al.
(author)
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Persistent pain after groin hernia surgery : a qualitative analysis of pain and its consequences for quality of life
- 2009
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In: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172 .- 1399-6576. ; 53:2, s. 236-246
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Journal article (peer-reviewed)abstract
- Despite a high prevalence of persistent groin pain after hernia repair, the specific nature of the pain and its clinical manifestation are poorly known. The aim of this study was to determine the type of post-herniorrhaphy pain and its influence on daily life. In order to assess long-term pain qualitatively and to explore how it affects quality of life, 100 individuals with persisting pain, identified in a cohort study of patients operated for groin hernia, were neurologically examined, along with 100 pain-free controls matched for age, gender and type of operation. The patients were asked to answer the SF-36 questionnaire, the hospital anxiety and depression scale, the Swedish Scales of Personality (SSP) and a standardised questionnaire for assessing everyday life coping. The patients were approached approximately 4.9 years after surgery. Twenty-two patients from the pain group had become pain free by the time of examination, whereas 76 patients still had pain, of whom 47 (68%) suffered from neuropathic pain and 11 from nociceptive pain. The remaining patients suffered from mixed pain, neuropathic and nociceptive, or were found to have another reason for pain. All dimensions of SF-36 were poorer for the pain group than the control group. Persistent post-herniorrhaphy pain is mainly neuropathic and has a substantial impact on health-related quality of life.
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| 16. |
- Kalliomäkia, Maija-Liisa, et al.
(author)
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Genetic susceptibility to postherniotomy pain : the influence of polymorphisms in the Mu opioid receptor, TNF-α, GRIK3, GCH1, BDNF and CACNA2D2 genes
- 2016
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In: Scandinavian Journal of Pain. - : Elsevier. - 1877-8860 .- 1877-8879. ; 12, s. 1-6
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Journal article (peer-reviewed)abstract
- Background and aims: Despite improvements in surgical technique, 5%–8% of patients undergoing herniorrhaphy still suffer from clinically relevant persistent postherniotomy pain. This is a problem at both individual and society levels. The aim of this study was to determine whether or not a single nucleotide polymorphism in a specific gene contributes to the development of persistent pain after surgery.Methods: One hundred individuals with persistent postherniotomy pain, along with 100 without pain matched for age, gender and type of surgery were identified in a previous cohort study on patients operated for groin hernia. All patients underwent a thorough sensory examination and blood samples were collected. DNA was extracted and analysed for single nucleotide polymorphism in the Mu opioid receptor, TNF-α, GRIK3, GCH1, BDNF and CACNA2D2 genes.Results: Patients with neuropathic pain were found to have a homozygous single nucleotide polymorph in the TNF-α gene significantly more often than pain-free patients (P = 0.036, one-tailed test).Conclusions: SNP in the TNF-α gene has a significant impact on the risk for developing PPSP.Implications: The result suggests the involvement of genetic variance in the development of pain and this requires further investigation.
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| 17. |
- Kozyrev, Sergey V, et al.
(author)
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Functional variants in the B-cell gene BANK1 are associated with systemic lupus erythematosus
- 2008
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 40:2, s. 211-216
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Journal article (peer-reviewed)abstract
- Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease characterized by production of autoantibodies and complex genetic inheritance(1-3). In a genome-wide scan using 85,042 SNPs, we identified an association between SLE and a nonsynonymous substitution (rs10516487, R61H) in the B-cell scaffold protein with ankyrin repeats gene, BANK1. We replicated the association in four independent case-control sets (combined P = 3.7 x 10(-10); OR = 1.38). We analyzed BANK1 cDNA and found two isoforms, one full-length and the other alternatively spliced and lacking exon 2 (Delta 2), encoding a protein without a putative IP3R-binding domain. The transcripts were differentially expressed depending on a branch point-site SNP, rs17266594, in strong linkage disequilibrium (LD) with rs10516487. A third associated variant was found in the ankyrin domain (rs3733197, A383T). Our findings implicate BANK1 as a susceptibility gene for SLE, with variants affecting regulatory sites and key functional domains. The disease-associated variants could contribute to sustained B cell-receptor signaling and B-cell hyperactivity characteristic of this disease.
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| 18. |
- Sánchez, Elena, et al.
(author)
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Association of a CD24 Gene Polymorphism with Susceptibility to Systemic Lupus Erythematosus
- 2007
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In: Arthritis and Rheumatism. - : Wiley. - 0004-3591 .- 1529-0131. ; 56:9, s. 3080-3086
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Journal article (peer-reviewed)abstract
- Objective. To determine the potential role of the CD24 A57V gene polymorphism in systemic lupus erythematosus (SLE). Methods. We studied 3 cohorts of Caucasian patients and controls. The Spanish cohort included 696 SLE patients and 539 controls, the German cohort included 257 SLE patients and 317 controls, and the Swedish cohort included 310 SLE patients and 247 controls. The CD24 A57V polymorphism was genotyped by polymerase chain reaction, using a predeveloped TaqMan allele discrimination assay. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. Results. In the Spanish cohort there was a statistically significant difference in the distribution of the CD24 V allele between SLE patients and controls (OR 3.6 [95% CI 2.13-6.16], P < 0.0001). In addition, frequency of the CD24 V/V genotype was increased in SLE patients compared with controls (OR 3.7 [95% CI 2.16-6.34], P < 0.00001). We sought to replicate this association with SLE in a German population and a Swedish population. A similar trend was found in the German group. The CD24 V/V genotype and the CD24 V allele were more frequent in SLE patients than in controls, although this difference was not statistically significant. No differences were observed in the Swedish group. A meta-analysis of the Spanish and German cohorts demonstrated that the CD24 V allele has a risk effect in SLE patients (pooled OR 1.25 [95% Cl 1.08-1.46], P = 0.003). In addition, homozygosity for the CD24 V risk allele significantly increased the effect (pooled OR 2.1,9 [95% Cl 1.50-3.22], P = 0.00007). Conclusion. These findings suggest that the CD24 A57V polymorphism plays a role in susceptibility to SLE in a Spanish population.
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