| 1. |
- Gruber, Jan, et al.
(författare)
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Allantoin in human plasma, serum, and nasal-lining fluids as a biomarker of oxidative stress : avoiding artifacts and establishing real in vivo concentrations.
- 2009
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Ingår i: Antioxidants and Redox Signaling. - 1523-0864 .- 1557-7716. ; 11:8, s. 1767-1776
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Tidskriftsartikel (refereegranskat)abstract
- Urate is the terminal product of purine metabolism in primates, including humans. Urate is also an efficient scavenger of oxidizing species and is thought to be an important antioxidant in human body fluids. Allantoin, the major oxidation product of urate, has been suggested as a candidate biomarker of oxidative stress because it is not produced metabolically. Although urate is converted to allantoin under strongly alkaline pH, such conditions have been used in the past to facilitate extraction of allantoin. We evolved a method for the determination of allantoin concentrations in human plasma and serum by gas chromatography-mass spectrometry without such artifact. With this method, we show that alkaline conditions do indeed cause breakdown of urate, leading to significant overestimation of allantoin concentration in human samples. By using our alternative method, serum samples from 98 volunteers were analyzed, and allantoin levels were found to be significantly lower than was previously reported. The in vivo utility and sensitivity of our method was further evaluated in human nasal-lining fluids. We were able to demonstrate an ozone-induced increase in allantoin, in the absence of increases in either ascorbate or glutathione oxidation products.
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| 2. |
- Kasiman, Katherine, et al.
(författare)
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Common Familial Effects on Ischemic Stroke and Myocardial Infarction: A Prospective Population-Based Cohort Study
- 2014
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Ingår i: Frontiers in Cardiovascular Medicine. - : Frontiers Media SA. - 2297-055X. ; , s. 1-10-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:Recent genome-wide association studies suggest some overlap of genetic determinants of ischemic stroke (IS) and myocardial infarction (MI). This study aimed to assess shared familial risk between IS and MI in a large, population-wide cohort study.METHODS:Study participants free of IS and MI and their affected siblings were extracted from the Swedish Hospital Discharge and Cause of Death Registers between 1987 and 2007, forming an exposed sib-pair. They were matched by birth year of both siblings and calendar period to up to five unexposed sib-pairs. Stratified Cox regression analyses were used to assess familial risk of MI and IS in those exposed to having a sibling with IS (n = 31,659) and MI (n = 62,766), respectively, compared to unexposed (n = 143,728 and 265,974).RESULTS:The overall risk of MI when exposed to having a sibling with IS was statistically significantly increased (RR, 1.44; 95% CI, 1.34-1.55, p < 0.001) to a similar extent as risk of IS when exposed to having a sibling with MI (RR, 1.41; 95% CI, 1.32-1.50, p < 0.001). The familial risks were similar in full siblings for both groups (RR for MI, 1.46; 95% CI, 1.35-1.58, p < 0.001; and RR for IS, 1.40; 95% CI, 1.30-1.40, p < 0.001) and half siblings (RR for MI, 1.29; 95% CI, 1.05-1.59, p < 0.001; and RR for IS, 1.38; 95% CI, 1.16-1.65, p < 0.001).CONCLUSION:This large, population-wide study indicates that there is considerable overlap of familial risk between IS and MI.
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| 3. |
- Kasiman, Katherine, et al.
(författare)
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Familial effects on ischemic stroke : the role of sibling kinship, sex, and age of onset
- 2012
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Ingår i: Circulation. - 1942-325X .- 1942-3268. ; 5:2, s. 226-233
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Previous studies on familial risk of ischemic stroke have supported genetic influence on the disease incidence. This study aimed to characterize these familial effects in a nationwide population-based study by taking into account sibling relations, sex of siblings, and age of onset, with respect to ischemic stroke incidence.METHODS AND RESULTS: Incident ischemic stroke cases identified from the Swedish Hospital Discharge and Cause of Death Registers between 1987 and 2007 were linked to their stroke-free siblings (study participants), forming an exposed sib-pair. Each exposed sib-pair was matched up to 5 unexposed sib-pairs from the Multi-Generation Registry by birth and calendar years. Incident ischemic stroke risk was assessed using hazard estimates obtained from stratified Cox regression analyses. A total of 30 735 exposed and 152 391 unexposed study participants were included in the analyses. The overall risk of incident ischemic stroke when exposed was significantly increased (relative risk, 1.61; 95% confidence interval, 1.48-1.75; P<0.001). Familial risk was higher in full (relative risk, 1.64; 95% confidence interval, 1.50-1.81; P<0.001) than in half (relative risk, 1.41; 95% confidence interval, 1.10-1.82; P=0.007) siblings. Familial risk of early ischemic stroke almost doubled when exposed to early ischemic stroke (relative risk, 1.94; 95% confidence interval, 1.41-2.67; P<0.001).CONCLUSIONS: There was a 60% increased risk for ischemic stroke in individuals having a sibling with prior stroke. The familial effect was even higher for full-sibling relations. Familial effects were observed in both male and female individuals, and no differential effects depending on the sex of either of the siblings were found.
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| 4. |
- Kasiman, Katherine
(författare)
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The genetic and molecular markers of ischemic stroke : risk, prognosis, and treatment
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Stroke is a major cause of mortality and morbidity worldwide, with ischemic stroke (IS) being the predominant type. With the current ageing population, IS burden will inevitably escalate leading to increasing demand for more effective prevention, diagnosis, and treatment strategies. The overall aim of this thesis was to elucidate various factors affecting IS in different stages, from risk to prognosis and subsequently treatment, by exploring potential genetic and/or molecular markers of IS in the hope to better understand this complex multi-factorial vascular disease. In Study I, we estimated the familial risk of IS in a very large, nation-wide population-based study by exploring the effects of sibling kinship, sex, and age in the heritability of IS. We found a 60% increased risk for IS in individuals having a sibling with prior stroke, and the risk was stronger for full siblings compared to half siblings. Having a sibling with early IS doubled the risk of early IS. No sex differences were found in the familial inheritance of IS. In Study II, we assessed the common familial risk between IS and MI in a large, population-wide matched cohort study where we observed a 44% increased risk for MI in individuals having a sibling with prior IS and a 41% increased risk for IS in individuals having a sibling with prior MI, indicating shared familial aggregation between these two conditions. In Study III, we explored the utility of sub-acute C-reactive protein (CRP) measurement in the prediction of outcomes after IS in a large prospective cohort of Singaporean acute IS patients, and whether CRP addition improved a conventional prognostic model. Only CRP at high levels was significantly associated with outcomes independent of other risk factors. In addition, comparison of conventional prognostic models with and without CRP showed significantly better fit in predictor model improvement upon CRP addition. In Study IV, we examined whether the efficacy of B-vitamin in reducing total homocysteine (tHcy) was modified by ethnicity in a Singaporean IS population. The magnitude of reduction in tHcy with B-vitamin therapy did not differ between ethnic groups despite differences in dietary intake and genetic makeup. In conclusion, data from the Swedish registers showed that full siblings exposed to IS have a higher risk of IS compared to those unexposed, and that early exposure to IS doubled the risk of IS compared to those unexposed. Similar increased risks for MI and IS when exposed to IS and MI respectively suggested shared familial aggregation between these two conditions. Data from the Singapore IS patients cohorts suggested the potential added value of CRP measurement towards prediction of future outcomes, and that the effect of B-vitamins in lowering tHcy may be generalizable across Asian IS populations.
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