| 1. |
- Campus, G., et al.
(författare)
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Effect of a daily dose of Lactobacillus brevis CD2 lozenges in high caries risk schoolchildren
- 2014
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Ingår i: Clinical Oral Investigations. - : Springer Science and Business Media LLC. - 1432-6981 .- 1436-3771. ; 18:2, s. 555-561
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Tidskriftsartikel (refereegranskat)abstract
- A double-blind, randomised, placebo-controlled clinical trial was performed to validate the hypothesis that the use of lozenges containing Lactobacillus brevis CD2 (InersanA (R), CD Investments srl) may reduce plaque pH, salivary mutans streptococci (ms) and bleeding on probing, during a 6-week period, in a sample of high caries risk schoolchildren. A total of 191 children (aged 6-8 years), presenting two to three carious lesions and a salivary ms concentration of a parts per thousand yen10(5) CFU/ml, were enrolled and divided into two groups, an L. brevis CD2 lozenge group and a no L. brevis lozenge group, and examined at baseline (t(0)), after 3 weeks (t(1)), after 6 weeks of lozenge use (t(2)) and 2 weeks after the cessation of lozenge use (t(3)). Plaque pH was assessed using the microtouch technique following a sucrose challenge. The area under the curve (AUC(5.7) and AUC(6.2)) was recorded. Salivary ms were counted, and bleeding on probing was assessed. At t(0), the plaque-pH and ms concentration values were similar in both groups. Mean areas (AUC(5.7) and AUC(6.2)) were significantly greater in the control group at t(1), t(2) and t(3). L. brevis CD2 lozenges significantly reduced salivary ms concentrations and bleeding. The subjects from the test group showed a statistically significant decrease (p = 0.01) in salivary ms concentration. At t(2), a statistically significantly lower bleeding value was recorded in the test group compared with the control group (p = 0.02). Six weeks' use of lozenges containing L. brevis CD2 had a beneficial effect on some important variables related to oral health, including a reduction in plaque acidogenicity, salivary ms and bleeding on probing. (Trial Registration Number NCT01601145 08/21/2012).
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| 2. |
- Duits, Flora H., et al.
(författare)
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The cerebrospinal fluid "Alzheimer profile": Easily said, but what does it mean?
- 2014
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Ingår i: Alzheimer's & Dementia. - : Elsevier. - 1552-5260 .- 1552-5279. ; 10:6, s. 713-723
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Tidskriftsartikel (refereegranskat)abstract
- Background: We aimed to identify the most useful definition of the "cerebrospinal fluid Alzheimer profile," based on amyloid-beta(1-42) (A beta(42)), total tau, and phosphorylated tau (p-tau), for diagnosis and prognosis of Alzheimers disease (AD). Methods: We constructed eight Alzheimer profiles with previously published combinations, including regression formulas and simple ratios. We compared their diagnostic accuracy and ability to predict dementia due to AD in 1385 patients from the Amsterdam Dementia Cohort. Results were validated in an independent cohort (n = 1442). Results: Combinations outperformed individual biomarkers. Based on the sensitivity of the best performing regression formulas, cutoffs were chosen at 0.52 for the tau/A beta(42) ratio and 0.08 for the p-tau/A beta(42) ratio. Ratios performed similar to formulas (sensitivity, 91%-93%; specificity, 81%-84%). The same combinations best predicted cognitive decline in mild cognitive impairment patients. Validation confirmed these results, especially regarding the tau/A beta(42) ratio. Conclusions: A tau/A beta(42) ratio of greater than0.52 constitutes a robust cerebrospinal fluid Alzheimer profile. We recommend using this ratio to combine biomarkers.
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| 3. |
- Holmström, Therese E., et al.
(författare)
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Non-transactivational, dual pathways for LPA-induced Erk1/2 activation in primary cultures of brown pre-adipocytes
- 2010
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Ingår i: Experimental Cell Research. - : Elsevier BV. - 0014-4827 .- 1090-2422. ; 316:16, s. 2664-75
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Tidskriftsartikel (refereegranskat)abstract
- In many cell types, G-protein-coupled receptor (GPCR)-induced Erk1/2 MAP kinase activation is mediated via receptor tyrosine kinase (RTK) transactivation, in particular via the epidermal growth factor (EGF) receptor. Lysophosphatidic acid (LPA), acting via GPCRs, is a mitogen and MAP kinase activator in many systems, and LPA can regulate adipocyte proliferation. The mechanism by which LPA activates the Erk1/2 MAP kinase is generally accepted to be via EGF receptor transactivation. In primary cultures of brown pre-adipocytes, EGF can induce Erk1/2 activation, which is obligatory and determinant for EGF-induced proliferation of these cells. Therefore, we have here examined whether LPA, via EGF transactivation, can activate Erk1/2 in brown pre-adipocytes. We found that LPA could induce Erk1/2 activation. However, the LPA-induced Erk1/2 activation was independent of transactivation of EGF receptors (or PDGF receptors) in these cells (whereas in transformed HIB-1B brown adipocytes, the LPA-induced Erk1/2 activation indeed proceeded via EGF receptor transactivation). In the brown pre-adipocytes, LPA instead induced Erk1/2 activation via two distinct non-transactivational pathways, one G(i)-protein dependent, involving PKC and Src activation, the other, a PTX-insensitive pathway, involving PI3K (but not Akt) activation. Earlier studies showing LPA-induced Erk1/2 activation being fully dependent on RTK transactivation have all been performed in cell lines and transfected cells. The present study implies that in non-transformed systems, RTK transactivation may not be involved in the mediation of GPCR-induced Erk1/2 MAP kinase activation
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| 4. |
- Mattsson, Charlotte L, et al.
(författare)
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Caveolin-1-ablated mice survive in cold by nonshivering thermogenesis despite desensitized adrenergic responsiveness
- 2010
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Ingår i: American Journal of Physiology. Endocrinology and Metabolism. - : American Physiological Society. - 0193-1849 .- 1522-1555. ; 299:3, s. E374-83
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Tidskriftsartikel (refereegranskat)abstract
- Caveolin-1 (Cav1)-ablated mice display impaired lipolysis in white adipose tissue. They also seem to have an impairment in brown adipose tissue function, implying that Cav1-ablated mice could encounter problems in surviving longer periods in cold temperatures. To investigate this, Cav1-ablated mice and wild-type mice were transferred to cold temperatures for extended periods of time, and parameters related to metabolism and thermogenesis were investigated. Unexpectedly, the Cav1-ablated mice survived in the cold. There were no differences between Cav1-ablated and wild-type mice with regard to food intake, in behavior related to shivering, or in body temperature. The Cav1-ablated mice had a halved total fat content independently of acclimation temperature. There was no difference in brown adipose tissue uncoupling protein-1 (UCP1) protein amount, and isolated brown fat mitochondria were thermogenically competent but displayed 30% higher thermogenic capacity. However, the beta(3)-adrenergic receptor amount was reduced by about one-third in the Cav1-ablated mice at all acclimation temperatures. Principally in accordance with this, a higher than standard dose of norepinephrine was needed to obtain full norepinephrine-induced thermogenesis in the Cav1-ablated mice; the higher dose was also needed for the Cav1-ablated mice to be able to utilize fat as a substrate for thermogenesis. In conclusion, the ablation of Cav1 impairs brown adipose tissue function by a desensitization of the adrenergic response; however, the desensitization is not evident in the animal as it is overcome physiologically, and Cav1-ablated mice can therefore survive in prolonged cold by nonshivering thermogenesis.
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| 5. |
- Mattsson, Charlotte L, et al.
(författare)
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Differential involvement of caveolin-1 in brown adipocyte signaling : impaired beta3-adrenergic, but unaffected LPA, PDGF and EGF receptor signaling.
- 2010
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Ingår i: Biochimica et Biophysica Acta. - : Elsevier BV. - 0006-3002 .- 1878-2434. ; 1803:8, s. 983-9
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Tidskriftsartikel (refereegranskat)abstract
- Caveolae and caveolin have been implicated as being involved in the signal transduction of many receptors, including the EGF, PDGF, LPA and beta3-adrenergic receptors. To investigate the role of caveolin-1 (Cav1) in these signaling pathways in brown adipose tissue, primary brown adipocyte cultures from Cav1-ablated mice and wild-type mice were investigated. In pre-adipocytes, Cav1-ablation affected neither the G-protein coupled LPA receptor signaling to Erk1/2, nor the receptor tyrosine kinases PDGF- or EGF-receptor signaling to Erk1/2. Mature primary Cav1-/- brown adipocytes accumulated lipids and expressed aP2 to the same extent as did wild-type cells. However, the cAMP levels induced by the beta3-adrenergic receptor agonist CL316,243 were lower in the Cav1-/- cultures, with an unchanged EC50 for CL316,243. Also the response to the direct adenylyl cyclase agonist forskolin was reduced. Thus, in brown adipocytes, Cav1 is apparently required for an intact response to adenylyl cyclase-linked agonists/activators, whereas other signaling pathways examined function without Cav1
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| 6. |
- Mattsson, Charlotte L., 1978-
(författare)
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Role of caveolin-1 in brown adipose tissue
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Caveolae are 50-100 nm invaginations in the plasma membrane. Caveolae and the protein caveolin-1 (Cav1) have been shown to be important in many signaling pathways in different cell types; however, in some cell types caveolae and Cav1 do not seem to affect the investigated signaling pathways. In my thesis, I have investigated the role of caveolin-1 (Cav1) in metabolism and b3-adrenergic, LPA-, EGF- and PDGF-receptor signaling in brown adipocytes. Brown adipose tissue is responsible for nonshivering thermogenesis. Recent studies have shown that not only infants but also adult man can have brown adipose tissue and that the presence is negatively correlated with both obesity and age. By understanding how signaling for proliferation and differentiation in brown adipocytes is regulated, it could be possible in the future to activate brown adipose tissue to combat obesity and the metabolic syndrome. In brown adipocytes, both epidermal growth factor (EGF) and platelet-derived growth factor (PDGF) were able to induce proliferation, which was dependent on Erk1/2 activation. However, EGF and PDGF utilized different pathways to activate Erk1/2, with EGF signaling partially occurring via a Src-pathway (not involving PI3K/PKC) and PDGF via a PI3K/PKC/Src-pathway. Furthermore, LPA receptors were able to activate Erk1/2 via two pathways, one Gi/PKC/Src-pathway and one PI3K-pathway. For these receptors, Cav1-ablation did not affect the agonist-induced Erk1/2 activation. Cav1 was, however, required for proper b3-adrenergic receptor (b3-AR) signaling to cAMP and for adenylyl cyclase activity. In Cav1-ablated mice, the adrenergic receptors are desensitized. However, this desensitization could be overcome physiologically, and the Cav1-ablated mice were therefore able to survive in prolonged cold by nonshivering thermogenesis. In conclusion, ablation of Cav1 affected certain signaling pathways in brown adipocytes, while other pathways were not affected or could be physiologically rescued.
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| 7. |
- Mattsson, Charlotte L., et al.
(författare)
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β₁-Adrenergic receptors increase UCP1 in human MADS brown adipocytes and rescue cold-acclimated β₃-adrenergic receptor-knockout mice via nonshivering thermogenesis
- 2011
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Ingår i: American Journal of Physiology. Endocrinology and Metabolism. - : American Physiological Society. - 0193-1849 .- 1522-1555. ; 301:6, s. E1108-E1118
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Tidskriftsartikel (refereegranskat)abstract
- With the finding that brown adipose tissue is present and negatively correlated to obesity in adult man, finding the mechanism(s) of how to activate brown adipose tissue in humans could be important in combating obesity, type 2 diabetes, and their complications. In mice, the main regulator of nonshivering thermogenesis in brown adipose tissue is norepinephrine acting predominantly via β(3)-adrenergic receptors. However, vast majorities of β(3)-adrenergic agonists have so far not been able to stimulate human β(3)-adrenergic receptors or brown adipose tissue activity, and it was postulated that human brown adipose tissue could be regulated instead by β(1)-adrenergic receptors. Therefore, we have investigated the signaling pathways, specifically pathways to nonshivering thermogenesis, in mice lacking β(3)-adrenergic receptors. Wild-type and β(3)-knockout mice were either exposed to acute cold (up to 12 h) or acclimated for 7 wk to cold, and parameters related to metabolism and brown adipose tissue function were investigated. β(3)-knockout mice were able to survive both acute and prolonged cold exposure due to activation of β(1)-adrenergic receptors. Thus, in the absence of β(3)-adrenergic receptors, β(1)-adrenergic receptors are effectively able to signal via cAMP to elicit cAMP-mediated responses and to recruit and activate brown adipose tissue. In addition, we found that in human multipotent adipose-derived stem cells differentiated into functional brown adipocytes, activation of either β(1)-adrenergic receptors or β(3)-adrenergic receptors was able to increase UCP1 mRNA and protein levels. Thus, in humans, β(1)-adrenergic receptors could play an important role in regulating nonshivering thermogenesis.
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| 8. |
- Mattsson, Niklas, 1979, et al.
(författare)
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Reference measurement procedures for Alzheimer's disease cerebrospinal fluid biomarkers: definitions and approaches with focus on amyloid β42.
- 2012
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Ingår i: Biomarkers in medicine. - : Future Medicine Ltd. - 1752-0371 .- 1752-0363. ; 6:4, s. 409-17
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Tidskriftsartikel (refereegranskat)abstract
- Cerebrospinal fluid (CSF) biomarkers for Alzheimer's disease (AD) are increasingly used in clinical settings, research and drug trials. However, their broad-scale use on different technology platforms is hampered by the lack of standardization at the level of sample handling, determination of concentrations of analytes and the absence of well-defined performance criteria for in vitro diagnostic or companion diagnostic assays, which influences the apparent concentration of the analytes measured and the subsequent interpretation of the data. There is a need for harmonization of CSF AD biomarker assays that can reliably, across centers, quantitate CSF biomarkers with high analytical precision, selectivity and stability over long time periods. In this position paper, we discuss reference procedures for the measurement of CSF AD biomarkers, especially amyloid β42 and tau. We describe possible technical approaches, focusing on a selected reaction monitoring mass spectrometry assay as a candidate reference method for quantification of CSF amyloid β42.
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| 9. |
- Mattsson, Niklas, 1979, et al.
(författare)
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The Alzheimer's Association external quality control program for cerebrospinal fluid biomarkers.
- 2011
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Ingår i: Alzheimer's & dementia : the journal of the Alzheimer's Association. - : Wiley. - 1552-5279. ; 7:4
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Tidskriftsartikel (refereegranskat)abstract
- The cerebrospinal fluid (CSF) biomarkers amyloid β (Aβ)-42, total-tau (T-tau), and phosphorylated-tau (P-tau) demonstrate good diagnostic accuracy for Alzheimer's disease (AD). However, there are large variations in biomarker measurements between studies, and between and within laboratories. The Alzheimer's Association has initiated a global quality control program to estimate and monitor variability of measurements, quantify batch-to-batch assay variations, and identify sources of variability. In this article, we present the results from the first two rounds of the program.
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| 10. |
- Petersson, Jesper, et al.
(författare)
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Albitization and quartz dissolution in Paleoproterozoic metagranite, central Sweden - Implications for the disposal of spent nuclear fuel in a deep geological repository
- 2012
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Ingår i: Lithos. - : Elsevier BV. - 0024-4937 .- 1872-6143. ; 148, s. 10-26
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Tidskriftsartikel (refereegranskat)abstract
- Hydrothermal alteration resulting in albitization and quartz dissolution has been identified in Paleoproterozoic metagranites down to - 1000 m elevation at Forsmark, Sweden. The alteration features were discovered during investigations to locate a site for the disposal of spent nuclear fuel in a deep geological repository. In general, albitization occurs extensively, but it is also observed locally adjacent to minor intrusive bodies of amphibolite. The altered rocks show a marked decrease in K-feldspar and an increase in quartz relative to the unaltered equivalents, resulting in an epitonalitic composition. Plagioclase is metamorphic in character and generally richer in albite than in the unaltered rocks. It is inferred that albitization was triggered by the input of basic or intermediate melts into the crust during igneous activity close to the peak of regional metamorphism at 1.87-1.86 Ga. The mineralogy of the epitonalites gives rise to an increased thermal conductivity and, thereby, a positive influence for the design and safety of a deep geological repository for spent nuclear fuel. However, the increased frequency of low conductive amphibolite in the albitized volumes, consistent with the proposed mechanism for alteration, gives a negative influence. In sharp contrast to the albitization, a majority of the occurrences of quartz dissolution, which resulted in the formation of episyenite, are located along fracture zones. Quartz dissolution took place between or after 1.8-1.7 Ga, when the bedrock was able to respond to deformation in a brittle manner. Most of the vugs left after the removal of quartz are, to a variable extent, refilled by hydrothermal assemblages, including quartz, albite, K-feldspar, hematite, chlorite and calcite. The geometry and spatial distribution of episyenite argue against an extreme fluid/rock ratio and it is inferred that the fluids had at least a moderate salinity with a temperature in excess of 300 degrees C. The dissolution process was promoted by the generation of secondary permeability localized in columnar or pipe-like volumes. The close spatial connection to fracture zones provides a basis to avoid bedrock affected by this type of alteration and, thereby, reduce the negative mechanical and hydrogeological aspects for a deep geological repository. (C) 2012 Elsevier B.V. All rights reserved.
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