| 1. |
- Arfvidsson, Berndt, et al.
(författare)
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S100B concentrations increase perioperatively in jugular vein blood despite limited metabolic and inflammatory response to clinically uneventful carotid endarterectomy
- 2015
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Ingår i: Clinical Chemistry and Laboratory Medicine. - : Walter de Gruyter GmbH. - 1434-6621 .- 1437-4331. ; 53:1, s. 111-117
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Tidskriftsartikel (refereegranskat)abstract
- Background: Our aim was to test the hypothesis that metabolic and inflammatory responses of the brain perioperatively during carotid endarterectomy (CEA) might affect blood brain barrier (BBB) integrity.Methods: Twenty patients with >70% stenosis of internal carotid artery (ICA) were prospectively included. Surgery was performed under general anaesthesia. Blood was sampled from ipsilateral internal jugular vein and radial artery: just before, during, and after ICA clamping S100B protein, glucose, lactate, 20 amino acids, and key cytokines were analysed.Results: Jugular vein S100B increased during clamping and reperfusion, while a marginal systemic increase was recorded, unrelated to stump pressure during clamping. Glucose increased during clamping in jugular vein blood and even more systemically, while jugular lactate values were higher than systemic values initially. Most amino acids did not differ significantly between jugular vein and systemic levels: glutamic acid and aspartic acid decreased during surgery while asparagine increased. Jugular vein interleukin (IL)-6 showed a transient non-significant increase during clamping and decreased systemically. IL-8 and IL-10 increased over time.Conclusions: Rising jugular vein S100B concentrations indicated reduced BBB integrity, and marginal secondary increase of S100B systemically. Limited ischaemic effects on the brain during cross-clamping, unrelated to S100B concentrations, were confirmed by lower brain glucose levels and higher lactate levels than in systemic blood. The lack of increased jugular vein glutamic acid disproves any major ischaemic brain injury following CEA. The inflammatory response was limited, did not differ greatly between jugular and systemic blood, and was unrelated to S100B.
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| 2. |
- Börjel, Anna K., et al.
(författare)
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Novel mutations in the 5'-UTR of the FOLR1 gene
- 2006
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Ingår i: Clinical Chemistry and Laboratory Medicine. - 1434-6621 .- 1437-4331. ; 44:2, s. 161-167
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Tidskriftsartikel (refereegranskat)abstract
- We have previously reported two novel mutations in the 5'-untranslated region (UTR) of the gene for folate receptor-alpha (FOLR1). In our search for additional mutations, 92 patient samples with elevated levels of homocysteine were screened by single-strand conformation polymorphism (SSCP) between nt -425 and -782, and -712 and -1110. Between nt -425 and -782 we did not find any mutations. Between nt -712 and -1110 there were three novel mutations. One subject had two mutations very close to each other, c.-856C>T and c.-921T>C. Two subjects had a c.-1043G>A mutation. To get an idea of the prevalence of FOLR1 mutations in an unselected population, we also screened 692 healthy school children for mutations. In this cohort, between nt -188 and +272 we discovered one novel mutation, a single nucleotide substitution, c.-18C>T, in addition to five children with the 25-bp deletion mutation previously described by us. Thus, so far we have discovered six novel mutations in the 5'-UTR region of the gene for folate receptor-alpha. We genotyped all 17 subjects with a FOLR1 mutation for the methylenetetrahydrofolate reductase (MTHFR) 677C>T polymorphism, and developed new single-nucleotide polymorphism (SNP) genotyping protocols for MTHFR 1298A>C and 1793G>A utilising Pyrosequencing technology. None of the 17 subjects had the 677TT genotype, which ruled out this as a cause of elevated homocysteine levels, which was observed in some of the subjects. Further studies of mutations in the 5'-UTR of FOLR1, and in particular of their interplay with folate intake status, are warranted.
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| 3. |
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| 4. |
- Hultdin, Johan, et al.
(författare)
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Prospective study of first stroke in relation to plasma homocysteine and MTHFR 677C > T and 1298A > C genotypes and haplotypes : evidence for an association with hemorrhagic stroke
- 2011
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Ingår i: Clinical Chemistry and Laboratory Medicine. - Berlin : Walter de Gruyter. - 1434-6621 .- 1437-4331. ; 49:9, s. 1555-1562
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Tidskriftsartikel (refereegranskat)abstract
- Background: Abnormalities in homocysteine metabolism have been suggested as risk factors for stroke. The aim of this prospective study was to examine whether total plasma homocysteine concentration (tHcy) and its main genetic determinant, methylene tetrahydrofolate reductase (MTHFR) polymorphisms, were associated with first ischemic or hemorrhagic stroke.Methods: This was a nested case-referent study of 321 ischemic and 60 hemorrhagic stroke cases, defined by WHO MONICA criteria and each matched with two event-free referents for sex, age, cohort, recruitment date and geographical area. All subjects were from the population-based Northern Sweden Health and Disease Study cohorts. Odds ratios were determined by conditional logistic regression.Results: The mean follow-up time was 4.2 years. Both tHcy and MTHFR were independent predictors of hemorrhagic stroke in multivariate models including body mass index, hypertension and, for MTHFR, tHcy [OR for the highest vs. lowest tHcy quartile 8.13 (95% CI 1.83-36.1), p(trend)=0.002; OR for MTHFR 677TT vs. 677CC genotype 3.62 (95% CI 0.77-17.0), p(trend)=0.040]. Haplotype analyses confirmed that the MTHFR 677T-1298A haplotype was positively associated with hemorrhagic stroke [OR 1.81 (95% CI 1.09-3.00), p=0.022], whereas the MTHFR 677C-1298C haplotype was not significantly related to either hemorrhagic or ischemic stroke. Neither tHcy nor the MTHFR polymorphisms were significant predictors of ischemic stroke.Conclusion: Both elevated plasma homocysteine levels and the MTHFR 677T allele are indicators of increased risk of hemorrhagic stroke in the northern Swedish population.
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| 5. |
- Lind, Marcus, et al.
(författare)
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High homocysteine and low folate plasma concentrations are associated with cardiovascular events but not bleeding during warfarin treatment
- 2016
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Ingår i: Clinical Chemistry and Laboratory Medicine. - : Walter de Gruyter GmbH. - 1434-6621 .- 1437-4331. ; 54:12, s. 1981-1986
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Tidskriftsartikel (refereegranskat)abstract
- Background: Previous studies have shown that homocysteine and folate levels in plasma are associated with risk for cardiovascular events and mortality. The aim of this study was to investigate if plasma concentrations of total homocysteine and folate can predict major bleeding, cardiovascular events, and all-cause mortality in patients being treated with warfarin. Methods: In a longitudinal cohort study, 719 patients who were taking warfarin were followed for 3001 treatment years. The following were recorded and classified: major bleeding; cardiovascular events including stroke, arterial emboli, and myocardial infarction (MI); and mortality. Blood samples collected at baseline were analysed for plasma homocysteine and folate levels. Results: After adjustment for age, C-reactive protein, and creatinine, high homocysteine levels were associated with cardiovascular events [hazard ratio (HR) 1.23 per standard deviation (SD); 95% confidence interval (CI): 1.03-1.47], MI (HR 1.38 per SD; 95% CI: 1.03-1.85), and all-cause mortality (HR 1.41 per SD; 95% CI: 1.19-1.68). The highest tertile of folate compared to the lowest tertile was associated with decreased risk for both cardiovascular events (HR 0.64; 95% CI: 0.43-0.91) and MI (HR 0.45; 95% CI: 0.21-0.97). There was no association between major bleeding and homocysteine or folate levels. Conclusions: In patients receiving warfarin treatment, high homocysteine and low folate plasma concentrations are associated with increased risk for cardiovascular events but not major bleeding. For homocysteine levels, there is also an association with all-cause mortality.
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| 6. |
- Nilsson, Torbjörn K., et al.
(författare)
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Simultaneous genotyping of the three lactose tolerance-linked polymorphisms LCT –13907C>G, LCT –13910C>T and LCT –13915T>G with Pyrosequencing™ technology
- 2008
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Ingår i: Clinical Chemistry and Laboratory Medicine. - Berlin : Walter de Gruyter. - 1434-6621 .- 1437-4331. ; 46:1, s. 80-84
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Tidskriftsartikel (refereegranskat)abstract
- Background: We required a new genotyping method for the diagnosis of adult hypolactasia, which would allow the simultaneous genotyping of three known polymorphic loci linked to lactose tolerance (LCT –13907C>G, LCT –13910C>T and LCT –13915T>G) in a single PCR/pyrosequencing test run.Method: We utilized Pyrosequencing™ technology, a DNA-sequence-by-synthesis technique.Results: The developed Pyrosequencing™ method allowed genotyping of the three loci LCT –13907C>G, LCT –13910C>T and LCT –13915T>G in a single PCR/pyrosequencing test run. A separate Pyrosequencing™ assay was developed for genotyping of the LCT –14010G>C mutation. The methods were evaluated in 116 clinical samples from patients of non-European descent, sent to the laboratory for diagnosis of adult hypolactasia. The “African” mutations LCT –13907C>G and LCT –13915T>G were found in subjects originating not only from Somalia, Ethiopia and Eritrea but also in Arabs and Iranians. Several compound heterozygotes LCT –13907CG/–13915TG were found among Ethiopian, Eritrean and Somalian subjects. No subject with the LCT –14010G>C mutation was found among the studied subjects. Advantages compared to the other genotyping methods are less staff hands-on time than, e.g., restriction fragment length polymorphism (RFLP) analyses, avoiding radioactivity as in the originally described isotope-minisequencing and in addition, Pyrosequencing™ is a direct DNA sequencing technique which gives unambiguous genotyping results as well as some redundant sequence information beyond the single nucleotide polymorphism (SNP) position, which serves as a valuable internal control obtained for each sample.Conclusions: Pyrosequencing™ is a robust genotyping modality suitable for clinical genotyping of patients not only of European, but also of African or Middle Eastern descent, who may harbor any combination of the three LCT mutations, LCT –13907C>G, LCT –13910C>T, LCT –13915T>G.
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