| 61. |
- Karlsson, Jan-Olof, 1944, et al.
(author)
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Inhibition of Glycogen Synthase Kinase (GSK-3) Protects Against Oxidative Stress and Attenuates Apoptosis in Human Lens Epithelial Cells and the Mouse Lens in Organ Culure
- 2005
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In: Invest. Ophthalmol. Vis. Sci.. ; 46:5, s. 3867-
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Conference paper (peer-reviewed)abstract
- Purpose: GSK-3 may regulate Wnt signaling, gene expression, the cell cycle, cell differentiation and apoptosis. Inhibition of GSK-3 can be obtained via the structurally unrelated substances lithum or Kenpaullone. The lens and the lens epithelial cells are excellent models to study the role of this enzyme. Methods: Primary cultures of human lens epithelial cells (HLEC) or the mouse lens in organ culture were exposed to the GSK-3 inhibitors lithium (2 mM) or Kenpaullone (2 {micro}M) for times upp to 24h.The cells were, before or after treatment, placed in medium containing fluorogenic indicators of oxidative damage. DCFH-DA was used to assay peroxides, mitochondrial function was evaluated with Rhodamine 123 and JC-1, monochlorobimane was used to assay intracellular glutathione (GSH) levels, Proteolytic activities were assayed, on line, with cell-permeable fluorogenic substrates.Proteasome and calpain activities were assayed with LLVY-AMC, Cathepsin B with RR-AMC or FR-AMC. Metalloproteases were assayed with AAF-AMC. Caspase-3, 8 and 9 were assayed in cell extracts with DEVD-, IETD- or LEHD-AMC, respectively. Results: The mitochondrial membrane potential and the level of GSH increased by 10% after treatment of HLEC with Li or Kenpaullone for 24h. No change was observed for peroxide production. The basal (low) level of caspase-3 activity was decreased by at least 20%. No significant effects were found concerning caspase-8 or 9 activities. No effect was observed on the activity of calpain, the proteasome, metalloproteases and cathepsin D/E activity.The whole mouse lens in organ culture showed essentially the same elevated mitochondrial potential. The GSH increase was even more evident in the whole lens preparation. Conclusions: Inhibition of GSK-3 may protect against oxidative stress (and cataract) via prevention of MPT induction and attenuate apoptosis in HLEC.
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| 62. |
- Kondziella, Daniel, 1976, et al.
(author)
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Hypertension in spontaneously hypertensive rats occurs despite low plasma levels of homocysteine
- 2008
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In: Physiological Research. - 0862-8408. ; 57:3, s. 487-490
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Journal article (peer-reviewed)abstract
- Hyperhomocysteinemia has been suggested to induce hypertension due to its role in endothelial dysfunction. However, it remains controversial whether homocysteine and hypertension are truly causally related or merely loosely associated. To test the hypothesis that hyperhomocysteinemia occurs in Spontaneously Hypertensive Rats (SHR) we measured plasma levels of homocysteine in 10 male adult SHR and in 10 normotensive controls using Ion Exchange Chromatography. In addition, plasma concentrations of the 22 most common amino acids were measured to explore the relation of homocysteine with amino acid metabolism. Plasma levels of homocysteine were significantly lower in SHR (4.1 micromol/L +/-0.1) than in controls (7.2 micromol/L +/- 0.3; p<0.00001). The amounts of aminobutyric acid (ABU), alanine, citrulline and valine were decreased as well, whereas we found increased levels of aspartate, glutamate, glutamine, histidine and ornithine. Thus, contrary to our hypothesis, hypertension in SHR occurs despite low plasma levels of homocysteine. We provide a new hypothesis whereby reduced conversion of arginine to citrulline is related to increased ornithine levels, but decreased bioavailability of nitric oxide, resulting in impaired blood vessel relaxation and hypertension. In conclusion, our findings do not necessarily exclude that homocysteine and hypertension might be pathophysiologically connected, but corroborate the notion that hypertension can arise due to mechanisms independent of high homocysteine levels.
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| 63. |
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| 64. |
- Landgren, Sara, 1980, et al.
(author)
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No Association of VEGF Polymorphims with Alzheimer's Disease
- 2010
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In: NeuroMolecular Medicine. - : Springer Science and Business Media LLC. - 1535-1084 .- 1559-1174. ; 12:3, s. 224-228
-
Journal article (peer-reviewed)abstract
- The vascular hypothesis of Alzheimer's disease (AD) has brought the vascular endothelial growth factor (VEGF) into focus. The genomic region including the VEGF gene has been linked to AD and single nucleotide polymorphisms (SNPs) of the VEGF have in previous studies been associated with AD risk. To further evaluate these findings, we genotyped two SNPs in the VEGF gene (rs699947 [-2578]) and rs1570360 [-1154]) by TaqMan Allelic Discrimination in a study sample including AD patients (n = 801) and controls (n = 286). In a subgroup of the population these SNPs were analyzed in relation to APOE epsilon 4 genotype, to cerebrospinal fluid biomarkers (T-tau, P-tau, and beta(42)-Amyloid) as well as to neuropathological markers for AD (neurofibrillary tangles and senile plaques). No significant associations with risk for AD or any of the studied biomarkers could be found in this study, thus not supporting VEGF as being a major risk gene for AD.
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| 65. |
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| 66. |
- Lehtinen-Jacks, Susanna, et al.
(author)
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Serum 25-hydroxy vitamin D levels in middle-aged women in relationship to adiposity and height trajectories over three decades
- 2016
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In: European Journal of Clinical Nutrition. - : Springer Science and Business Media LLC. - 0954-3007 .- 1476-5640. ; 70:6, s. 709-14
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Journal article (peer-reviewed)abstract
- BACKGROUND/OBJECTIVES: The long-term chronology of the association between low serum concentrations of 25-hydroxy vitamin D (25(OH)D) and weight status is unclear. We examined whether lower 25(OH)D in middle-aged women drives upwards the weight, body mass index (BMI) and waist-hip ratio (WHR) over the next 32 years, and whether higher 25(OH)D might predict less decline in the mid- to late-life height trajectory. SUBJECTS/METHODS: The Population Study of Women in Gothenburg started in 1968-1969 (the baseline) in 38-60-year-old women residing in Gothenburg, Sweden. Anthropometric measures were taken at baseline and 4 re-examinations until 2000-2003. Levels of 25(OH)D were analyzed in serum stored since baseline in 1227 (84%) women. Repeated measures analyses were used to model associations between 25(OH)D (dichotomized, cut point 51.45nmol/l) at baseline and anthropometric trajectories, adjusting for fixed and time-dependent covariates. RESULTS: At baseline, mean BMI was 25.2kg/m2 in women with low 25(OH)D and 23.8kg/m2 in the remaining women (P<0.001), but this difference did not increase over 32 years and longitudinal differences were explained by the baseline BMI. Similar results were observed for weight and WHR. In contrast, no association was seen for height at baseline or longitudinally. CONCLUSIONS: No relationship was observed between 25(OH)D height trajectory, but lower 25(OH)D was associated with higher BMI, weight and WHR differences that were maintained over three decades. This provides no evidence for the direction of causality, but for a life-long difference in adiposity-related measures according to the 25D level in middle-aged women.
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| 67. |
- Leu, Monica, 1977, et al.
(author)
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Quality Assessment of 25(OH)D, Insulin, Total Cholesterol, Triglycerides, and Potassium in 40-Year-Old Frozen Serum
- 2015
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In: Epidemiology Research International. - : Hindawi Limited. - 2090-2980 .- 2090-2972. ; 2015
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Journal article (peer-reviewed)abstract
- Background: Many longitudinal epidemiological studies collect specimens into biobanks to investigate how biomarkers predict future disease. In 1968-1969, the Population Study of Women in Gothenburg (PSWG) established a biobank. Objective: To examine the validity of 25-hydroxyvitamin D (25(OH)D), total cholesterol, triglycerides, insulin and potassium after 40 years of storage at -20⁰C in terms of relative and absolute agreement. The quality of these markers under such condition has not been previously investigated. Methods: Baseline- and re-measured levels were compared in selected samples through percentage change, correlation and regression. 25(OH)D levels, not assessed at baseline, were compared by season, by BMI and longitudinally over six years. Results: Despite some lack of absolute agreement, Spearman correlations were >0.7 and statistically significant for all biomarkers. The 1968-1969 25(OH)D correlated with BMI (r=-0.45, p=0.05) and with levels six years later (r=0.85, p<0.001). Summer 25(OH)D was higher than winter 25(OH)D (p=0.02). Conclusion: For all markers, baseline- and re-measured levels exhibited high relative agreement. 25(OH)D was comparable with expected levels on fresh blood and varied with season. In future studies, PSWG individuals will be ranked according to these markers in order to follow incidence of disease.
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| 68. |
- Lindström, Johan, 1984, et al.
(author)
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Cerebrospinal fluid viral load and biomarkers of neuronal and glial cells in Ramsay Hunt syndrome.
- 2016
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In: The European journal of neuroscience. - : Wiley. - 1460-9568 .- 0953-816X. ; 44:11, s. 2944-2949
-
Journal article (peer-reviewed)abstract
- Reactivation of varicella zoster virus (VZV) can manifest with facial palsy diagnosed as Ramsay Hunt Syndrome (RHS) or Ramsay Hunt Syndrome zoster sine herpete (RHS-ZSH). These syndromes are associated with poor prognosis despite treatment with antivirals and corticosteroids. Concentrations of biomarkers such as neurofilament protein (NFL), S-100β protein and glial fibrillary acidic protein (GFAp) have previously been measured in cerebrospinal fluid (CSF) to assess neuronal damage and glial pathology. We employed immunochemical methods to measure concentrations of NFL, S-100β protein and GFAp in CSF from patients with RHS (n=15) and RHS-ZSH (n=13) diagnosed by detection of VZV DNA in the CSF by quantitative PCR, and compared with a control group (n=52). The biomarker concentrations were correlated with CSF viral load and outcome measured by House-Brackmann score. NFL and GFAp concentrations were increased compared with controls (P=0.008 and P=0.04), while S-100β levels were decreased. This pattern was more pronounced in patients with RHS compared to the patients with RHS-ZSH (NS and P=0.028). The amount of viral DNA in CSF correlated with increased GFAp (P=0.003) and NFL (P=0.006). No correlations were found between biomarker concentrations and patient outcome. Patients with facial palsy caused by VZV had biochemical signs of neuronal damage and astrogliosis. High amounts of viral DNA may be associated with the degree of damage on neuronal and astroglial cells. Prospective studies are warranted to elucidate the association of elevated biomarkers in the CSF and outcome assessed by more sensitive tests.
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| 69. |
- Lindström, Johan, 1984, et al.
(author)
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CXCL13 in patients with facial palsy caused by varicella zoster virus and Borrelia burgdorferi: a comparative study.
- 2020
-
In: Diagnostic microbiology and infectious disease. - : Elsevier BV. - 1879-0070 .- 0732-8893. ; 98:1
-
Journal article (peer-reviewed)abstract
- High cerebrospinal fluid (CSF) concentrations of the chemokine CXCL13 have been associated with Lyme neuroborreliosis (LNB), and have recently been studied as a potential diagnostic marker. It has proven difficult to establish a reliable diagnostic cut-off, possibly in part due to heterogenicity of case-control groups. Our purpose was to investigate CSF CXCL13 concentrations in patients with similar clinical presentations, facial palsy. We retrospectively included patients with facial palsy associated with LNB (n=21), or varicella zoster virus (VZV) (n=26). Median CXCL13 concentrations were significantly higher in patients with LNB facial palsy compared to VZV facial palsy. Receiver-operating characteristic analyses yielded an optimal cut-off concentration at 34.5pg/mL (sensitivity 85.7%, specificity of 84.6%), lower than that in previous studies. Although the analysis has potential, it is still not adequately established that CXCL13 provides additional, clinically useful, diagnostic information over current recommendations.
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| 70. |
- Makitalo, S., et al.
(author)
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The cerebrospinal fluid biomarker profile in an HIV-infected subject with Alzheimer's disease
- 2015
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In: Aids Research and Therapy. - : Springer Science and Business Media LLC. - 1742-6405. ; 12
-
Journal article (peer-reviewed)abstract
- It is a challenge to differentiate between HIV-associated neurocognitive disorders (HAND) and other types of neurocognitive disease in the ageing HIV-infected population. Here we describe a 63 year old HIV-infected woman who had a history, neuropsychological test result, and PET examination consistent with characteristic Alzheimer's disease (AD). The cerebrospinal fluid (CSF) biomarker profile was analogous to the profile typically found in AD in HIV-negative patients with increased t-tau and p-tau, a decreased level of A beta 42 and normal levels of CSF neurofilament light protein and sAPP alpha and sAPP beta, distinctly different from findings in HIV-associated dementia (HAD). Assessment of CSF biomarkers may be a valuable tool for clinicians to distinguish between HAD and AD.
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