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- Aaseth, Jan, et al.
(author)
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The Aging Kidney-As Influenced by Heavy Metal Exposure and Selenium Supplementation
- 2021
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In: Biomolecules. - : MDPI. - 2218-273X. ; 11:8
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Journal article (peer-reviewed)abstract
- The aging process in the kidneys has been well studied. It is known that the glomerular filtration rate (GFR) declines with age in subjects older than 50-60 years. However, there is still insufficient knowledge regarding the response of the aged kidney to environmental toxicants such as mercury, cadmium, and lead. Here, we present a review on the functional decline and proposed mechanisms in the aging kidney as influenced by metal pollutants. Due to the prevalence of these toxicants in the environment, human exposure is nearly unavoidable. Further, it is well known that acute and chronic exposures to toxic metals may be detrimental to kidneys of normal adults, thus it may be hypothesized that exposure of individuals with reduced GFR will result in additional reductions in renal function. Individuals with compromised renal function, either from aging or from a combination of aging and disease, may be particularly susceptible to environmental toxicants. The available data appear to show an association between exposure to mercury, cadmium and/or lead and an increase in incidence and severity of renal disease in elderly individuals. Furthermore, some physiological thiols, as well as adequate selenium status, appear to exert a protective action. Further studies providing improved insight into the mechanisms by which nephrotoxic metals are handled by aging kidneys, as well as possibilities of therapeutic protection, are of utmost importance.
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3. |
- Abujrais, Sandy, et al.
(author)
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A sensitive method detecting trace levels of levonorgestrel using LC-HRMS
- 2019
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In: Contraception. - : Elsevier BV. - 0010-7824 .- 1879-0518. ; 100:3, s. 247-249
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Journal article (peer-reviewed)abstract
- Objective: To develop a high resolution mass spectrometry (HRMS) method to quantify levonorgestrel (LNG) in serum. Study design: Levonorgestrel was extracted using solid phase extraction and measured using liquid chromatography (LC) HRMS. Results: Low limit of quantification (LLOQ) was 25 pg/mL and low limit of detection (LLOD) was 12.5 pg/mL. Precision and accuracy bias were <10%. LNG in serum samples from Mirena® users ranged between 37 to 219 pg/mL (n=12). In eight out of 22 patients with suspected intrauterine device (IUD) expulsion LNG was detected (26–1272 pg/mL). Conclusion: A sensitive, fast and simple LC-HRMS method was developed to detect trace levels of LNG. © 2019 Elsevier Inc.
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4. |
- Adamsson, Viola, et al.
(author)
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Role of a prudent breakfast in improving cardiometabolic risk factors in subjects with hypercholesterolemia : a randomized controlled trial
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Journal article (other academic/artistic)abstract
- Background & Aims: It is unclear whether advising a prudent breakfast alone is sufficient to improve blood lipids and cardiometabolic risk factors in overweight hypercholesterolemic subjects.Methods: The aim of the present study was to investigate whether a prudent low-fat breakfast (PB) rich in dietary fiber lowers low-density lipoprotein cholesterol (LDL-C) and other cardiometabolic risk factors in subjects with elevated LDL-cholesterol levels. In a parallel, controlled, 12-week study, 79 healthy overweight subjects (all regular breakfast eaters) were randomly allocated to a group that received a PB based on Nordic foods provided ad libitum or a control group that consumed their usual breakfast. The PB was in accordance with national and Nordic nutrition recommendations and included oat bran porridge with low-fat milk or yogurt, bilberry or lingonberry jam, whole grain bread, low-fat spread, poultry or fatty fish, and fruit.Results: No differences were found in LDL-C, blood lipids, body weight, or glucose metabolism, but SAD, plasma CRP, and TNF-R2 were lower during PB compared with controls (p<0.05). In the overall diet, PB increased dietary fiber and b-glucan compared with controls (p<0.05).Conclusions: Advising a prudent breakfast for 3 months did not influence blood lipids, body weight, or glucose metabolism but reduced markers of visceral fat and inflammation.
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5. |
- Adamsson, Viola, et al.
(author)
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Role of a prudent breakfast in improving cardiometabolic risk factors in subjects with hypercholesterolemia : A randomized controlled trial
- 2015
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In: Clinical Nutrition. - : Elsevier BV. - 0261-5614 .- 1532-1983. ; 34:1, s. 20-26
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Journal article (peer-reviewed)abstract
- BACKGROUND & AIMS:It is unclear whether advising a prudent breakfast alone is sufficient to improve blood lipids and cardiometabolic risk factors in overweight hypercholesterolemic subjects. The aim of this study was to investigate whether a prudent low-fat breakfast (PB) rich in dietary fiber lowers low-density lipoprotein cholesterol (LDL-C) and other cardiometabolic risk factors in subjects with elevated LDL-cholesterol levels.METHODS:In a parallel, controlled, 12-week study, 79 healthy overweight subjects (all regular breakfast eaters) were randomly allocated to a group that received a PB based on Nordic foods provided ad libitum or a control group that consumed their usual breakfast. The primary outcome was plasma LDL-C. Secondary outcomes were other blood lipids, body weight, sagittal abdominal diameter (SAD), glucose tolerance, insulin sensitivity and inflammation markers (C-reactive protein [CRP] and tumor necrosis factor receptor-2 [TNF-R2]), and blood pressure. The PB was in accordance with national and Nordic nutrition recommendations and included oat bran porridge with low-fat milk or yogurt, bilberry or lingonberry jam, whole grain bread, low-fat spread, poultry or fatty fish, and fruit.RESULTS:No differences were found in LDL-C, other blood lipids, body weight, or glucose metabolism, but SAD, plasma CRP, and TNF-R2 decreased more during PB compared with controls (p < 0.05). In the overall diet, PB increased dietary fiber and β-glucan compared with controls (p < 0.05).CONCLUSIONS:Advising a prudent breakfast for 3 months did not influence blood lipids, body weight, or glucose metabolism but reduced markers of visceral fat and inflammation. The trial was registered in the Current Controlled Trials database (http://www.controlled-trials.com); International Standard Randomized Controlled Trial Number (ISRCTN): 84550872.
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6. |
- Ahlström, J. Zebialowicz, et al.
(author)
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Synthetic surfactant with a recombinant surfactant protein C analogue improves lung function and attenuates inflammation in a model of acute respiratory distress syndrome in adult rabbits
- 2019
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In: Respiratory Research. - : BMC. - 1465-9921 .- 1465-993X. ; 20
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Journal article (peer-reviewed)abstract
- AimIn acute respiratory distress syndrome (ARDS) damaged alveolar epithelium, leakage of plasma proteins into the alveolar space and inactivation of pulmonary surfactant lead to respiratory dysfunction. Lung function could potentially be restored with exogenous surfactant therapy, but clinical trials have so far been disappointing. These negative results may be explained by inactivation and/or too low doses of the administered surfactant. Surfactant based on a recombinant surfactant protein C analogue (rSP-C33Leu) is easy to produce and in this study we compared its effects on lung function and inflammation with a commercial surfactant preparation in an adult rabbit model of ARDS.MethodsARDS was induced in adult New Zealand rabbits by mild lung-lavages followed by injurious ventilation (V-T 20m/kg body weight) until P/F ratio<26.7kPa. The animals were treated with two intratracheal boluses of 2.5mL/kg of 2% rSP-C33Leu in DPPC/egg PC/POPG, 50:40:10 or poractant alfa (Curosurf (R)), both surfactants containing 80mg phospholipids/mL, or air as control. The animals were subsequently ventilated (V-T 8-9m/kg body weight) for an additional 3h and lung function parameters were recorded. Histological appearance of the lungs, degree of lung oedema and levels of the cytokines TNF alpha IL-6 and IL-8 in lung homogenates were evaluated.ResultsBoth surfactant preparations improved lung function vs. the control group and also reduced inflammation scores, production of pro-inflammatory cytokines, and formation of lung oedema to similar degrees. Poractant alfa improved compliance at 1h, P/F ratio and PaO2 at 1.5h compared to rSP-C33Leu surfactant.ConclusionThis study indicates that treatment of experimental ARDS with synthetic lung surfactant based on rSP-C33Leu improves lung function and attenuates inflammation.
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7. |
- Ahlström, Tommy, et al.
(author)
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Correlation between plasma calcium, parathyroid hormone (PTH) and the metabolic syndrome (MetS) in a community-based cohort of men and women
- 2009
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In: Clinical Endocrinology. - : Wiley. - 0300-0664 .- 1365-2265. ; 71:5, s. 673-678
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Journal article (peer-reviewed)abstract
- CONTEXT: In recent years, an association has been noted between several abnormalities that characterize the metabolic syndrome (MetS) and primary hyperparathyroidism (pHPT). These abnormalities include dyslipidaemia, obesity, insulin resistance and hypertension. The correlations between plasma calcium, parathyroid hormone (PTH) and the variables in the MetS in a normal population are still unclear.OBJECTIVE: To describe correlations between plasma calcium and PTH and the various abnormalities present in the MetS in a healthy population.DESIGN: We studied 1016 healthy individuals from the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) population of 70 years old, by means of plasma analyses of calcium, PTH, creatinine, lipids, insulin and glucose, as well as by standardized blood pressure measurements. Further, body mass index (BMI) and waist circumference were determined.RESULTS: The more National Cholesterol Education Program (NCEP) criteria for the MetS that were met, the higher the s-PTH and albumin-corrected s-calcium. Further, positive correlations between plasma calcium and BMI (P = 0.0003), waist circumference (P = 0.0009) and insulin resistance (P = 0.079) were found. PTH and BMI (P < 0.0001), waist circumference (P < 0.0001), systolic blood pressure (P = 0.0034), diastolic blood pressure (P = 0.0008), serum triglycerides (P = 0.0003) and insulin resistance (P = 0.0003) were positively correlated, whereas serum high density lipoproteins (HDL) (P = 0.036) and PTH were negatively correlated.CONCLUSIONS: We conclude that PTH correlates with several of the metabolic factors included in the MetS within a normocalcaemic population. In addition, individuals with mild pHPT present significantly more NCEP criteria for MetS. We postulate that increased levels of PTH in pHPT may be associated with the increased cardiovascular morbidity and mortality seen in pHPT.
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8. |
- Ahmed, Degmo Said, et al.
(author)
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Quantitative determination of cerebrospinal fluid bilirubin on a high throughput chemistry analyzer
- 2009
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In: Clinical laboratory. - 1433-6510. ; 55:7-8, s. 283-288
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Journal article (peer-reviewed)abstract
- BACKGROUND: Subarachnoid hemorrhage is a condition with high rates of mortality and morbidity. The diagnosis requires an urgent cerebral computed tomography scan and also a lumbar puncture if the scan fails to demonstrate intracranial blood. In Sweden the cerebrospinal fluid (CSF) is analyzed by spectrophotometric scanning for the presence of hemoglobin and bilirubin. The aim of the study was to develop a quantitative diazo reagent based analysis of cerebrospinal fluid bilirubin as a replacement for spectrophotometric scanning. METHODS: The CSF bilirubin assay on an Architect C8000 chemistry analyzer was compared with spectrophotometry using patient samples. RESULTS: The method correlates with spectrophotometry, has a good linearity and precision. CONCLUSIONS: Quantitative bilirubin measurement offers shorter turnaround times, simplifies the interpretation of the results and reduces work load in comparison with spectrophotometry.
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9. |
- Ahmed, Laeeq, et al.
(author)
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Predicting target profiles with confidence as a service using docking scores
- 2020
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In: Journal of Cheminformatics. - : Springer Nature. - 1758-2946. ; 12:1
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Journal article (peer-reviewed)abstract
- Background: Identifying and assessing ligand-target binding is a core component in early drug discovery as one or more unwanted interactions may be associated with safety issues. Contributions: We present an open-source, extendable web service for predicting target profiles with confidence using machine learning for a panel of 7 targets, where models are trained on molecular docking scores from a large virtual library. The method uses conformal prediction to produce valid measures of prediction efficiency for a particular confidence level. The service also offers the possibility to dock chemical structures to the panel of targets with QuickVina on individual compound basis. Results: The docking procedure and resulting models were validated by docking well-known inhibitors for each of the 7 targets using QuickVina. The model predictions showed comparable performance to molecular docking scores against an external validation set. The implementation as publicly available microservices on Kubernetes ensures resilience, scalability, and extensibility.
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10. |
- Akhter, Tansim, 1967-, et al.
(author)
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Artery Wall Layer Dimensions during Normal Pregnancy : A longitudinal study using non-invasive high-frequency ultrasound
- 2013
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In: American Journal of Physiology. Heart and Circulatory Physiology. - : American Physiological Society. - 0363-6135 .- 1522-1539. ; 304:2, s. H229-H234
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Journal article (peer-reviewed)abstract
- The vascular effects of normal pregnancy were investigated by estimating the intima and media thicknesses of the common carotid artery separately using 22MHz ultrasound (Collagenoson, Meudt, Germany) in 57 healthy women with normal pregnancies and pregnancy outcomes, in all three trimesters and at one year postpartum. A thick intima, thin media and high intima/media (I/M) ratio are signs of a less healthy artery wall. The mean artery wall layer dimensions remained fairly constant during pregnancy but the intima thickness and I/M thickness ratio appeared to improve (decrease) postpartum (p<0.001 for both). The cardiovascular risk parameters age, body mass index (BMI), and blood pressure in the first trimester were associated with higher I/M ratios, especially in the second trimester, whereas higher serum estradiol levels were significantly associated with a lower I/M ratio. Changes from the first to second trimesters in I/M ratio, taking into account differential changes in intima and media thickness, were significantly (p<0.05-0.001) associated with all risk parameters tested except age, which was associated with increased intima thickness (p=0.02). Associations with third trimester values and changes from first to third trimesters were similar but less apparent. Thus, fairly constant mean artery wall layer dimensions during pregnancy appeared to improve postpartum. However, higher age, BMI or blood pressure, and lower serum estradiol levels in the first trimester appeared to negatively affect the artery wall, strongly suggesting that pregnancy has negative vascular effects in some women. A less likely explanation involves possible adaptation to physiological changes during and after pregnancy.
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