| 1. |
- Boij, Roland, et al.
(author)
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Biomarkers of Coagulation, Inflammation, and Angiogenesis are Independently Associated with Preeclampsia
- 2012
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In: AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY. - : John Wiley and Sons. - 1046-7408 .- 8755-8920. ; 68:3, s. 258-270
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Journal article (peer-reviewed)abstract
- Problem Although preeclampsia has been associated with inflammation, coagulation, and angiogenesis, their correlation and relative contribution are unknown. Method of Study About 114 women with preeclampsia, 31 with early onset (EOP) and 83 with late onset preeclampsia (LOP), and 100 normal pregnant controls were included. A broad panel of 32 biomarkers reflecting coagulation, inflammation, and angiogenesis was analyzed. Results Preeclampsia was associated with decreased antithrombin, IL-4 and placental growth factor levels and with increased C3a, pentraxin-3, and sFlt-1 levels, with more marked differences in the EOP group. The Th1-associated chemokines CXCL10 and CXCL11 were significantly higher in the preeclampsia and EOP group than in controls, respectively. No correlations between the biomarkers were found in preeclampsia. Multivariate logistic regression tests confirmed the results. Conclusions Cytokines, chemokines and complement activation seem to be part of a Th1-like inflammatory reaction in preeclampsia, most pronounced in EOP, where chemokines may be more useful than cytokines as biomarkers. Biomarkers were not correlated suggesting partly independent or in time separated mechanisms.
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| 2. |
- Jakobsson, Jenny, et al.
(author)
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Large differences in testosterone excretion in Korean and Swedish men are strongly associated with a UDP-glucuronosyl transferase 2B17 polymorphism.
- 2006
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In: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 91:2, s. 687-93
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Journal article (peer-reviewed)abstract
- CONTEXT: The reproductive endocrinology in Asians and Caucasians is of great interest in view of large differences in prostate cancer rate and sensitivity to pharmacological male contraception. In addition, interpretation of certain antidoping tests is confounded by interethnic variation in androgen disposition. Uridine diphosphoglucuronosyl transferases have a key role in the homeostasis and metabolism of androgens. Recently a deletion polymorphism was detected in the UGT2B17 gene. OBJECTIVE: The objective of the study was to evaluate the contribution of the UGT2B17 deletion polymorphism to the interindividual and interethnic variation of androgen metabolism and excretion. METHODS AND RESULTS: Urine from 122 Swedish and 74 Korean healthy men was analyzed for several androgen glucuronides including testosterone. The distribution of the natural logarithms of urinary testosterone concentrations showed a distinct bimodal pattern in both groups, suggesting a monogenic inheritance. When the UGT2B17 genotypes were compared with urinary testosterone levels, all of the individuals of the UGT2B17 homozygous deletion/deletion genotype had no or negligible amounts of urinary testosterone. The deletion/deletion genotype was seven times more common in the Korean (66.7%) than the Swedish population (9.3%). In addition, the Swedes had significantly higher levels of serum testosterone, compared with the Koreans. CONCLUSIONS: Our results show that the UGT2B17 polymorphism is strongly associated with the bimodal distribution of the testosterone excretion and also with the large differences in testosterone excretion between Koreans and Swedes.
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| 3. |
- Klötz, Fia, et al.
(author)
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Criminality Among Individuals Testing Positive for the Presence of Anabolic Androgenic Steroids
- 2006
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In: Archives of General Psychiatry. - : American Medical Association (AMA). - 0003-990X .- 1538-3636. ; 63:11, s. 1274-1279
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Journal article (peer-reviewed)abstract
- CONTEXT: Observations suggest that the use of anabolic androgenic steroids (AAS) may trigger uncontrolled, violent rage. Other observations indicate that certain groups of criminals may use AAS with the intention of being capable of committing crime more efficiently. OBJECTIVE: To examine the proposed association between the use of AAS and criminality. DESIGN: A controlled retrospective cohort study of registered criminal activity among individuals tested for AAS use during the period of January 1, 1995, to December 31, 2001. SETTING: All individuals in Sweden who were tested for AAS use during this period. These individuals were referred for testing from both inpatient and outpatient clinics as well as from centers for treatment of substance abuse. PARTICIPANTS: Individuals testing positive for AAS (n=241), with those testing negative for AAS during the same period (n=1199) serving as the control group. MAIN OUTCOME MEASURES: The ratios (expressed as relative risk [RR]) of the incidences of several categories of crime in the 2 study groups. RESULTS: The risk of having been convicted for a weapons offense or fraud was higher among individuals testing positive for AAS than among those testing negative (RR, 2.090 and 1.511, respectively; 95% confidence interval [CI], 1.589-2.749 and 1.208-1.891, respectively) whereas there were no significant differences with respect to violent crimes (RR, 1.116; 95% CI, 0.981-1.269) or crimes against property (RR, 0.942; 95% CI, 0.850-1.044). When patients referred from substance abuse centers were excluded, a lower risk for crimes against property was observed for the individuals who tested positive for AAS (RR, 0.761; 95% CI, 0.649-0.893) and the risk for fraud in the 2 groups was equalized (RR, 1.117; 95% CI, 0.764-1.635). The increased risk for a weapons offense among the individuals testing positive for AAS remained virtually unchanged. CONCLUSIONS: In addition to the impulsive violent behavior previously shown to be related to AAS use, such use might also be associated with an antisocial lifestyle involving various types of criminality. However, the existence and nature of this possible association remain unclear and call for further investigation.
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| 4. |
- Lood, Yvonne, et al.
(author)
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Anabolic androgenic steroids in police cases in Sweden 1999-2009
- 2012
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In: Forensic Science International. - : Elsevier. - 0379-0738 .- 1872-6283. ; 219:1-3, s. 199-204
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Journal article (peer-reviewed)abstract
- Anabolic Androgenic Steroids (AAS) are considered drugs of abuse and are controlled substances in Sweden since 1999. Traditionally AAS have been used by elite athletes to enhance performance, but in recent years it has become an increasing problem outside elite sport among athletes, bodybuilders and criminals. Use of AAS is associated with psychiatric side effects such as aggression, depression and violent behavior. Supraphysiological doses and long term use can cause serious physical harm such as cardiovascular toxicity and even premature death. We investigated and evaluated the drug analytical findings in forensic cases from suspected perpetrators in cases from the police where a screening for AAS was requested to get information about the prevalence of AAS use and the occurrence of poly-drug abuse. The study was based on samples submitted from the police authorities to the Department of Forensic Toxicology in Sweden during the period 1999-2009. Urines were analyzed by methods based on GC-MS and LC-MS-MS. We also analyzed the prevalence of AAS use at the prison and probation services. A total number of 12,141 urine samples (6362 police cases and 5779 inmates) were analyzed and 33.5% of the cases from the police and 11.5% of the inmates were tested positive for AAS. The users of AAS were mainly in 99.2% men with a mean age of 26.2 +/- 6.2 years whereas the women were 29.5 +/- 6.5 years old. The most frequently used AAS was nandrolone followed by testosterone and methandienone. Other illicit and licit drugs were detected in 60% of the cases from the police, strongly indicating a frequent poly-drug abuse among users of AAS.
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| 5. |
- Lönnberg, Maria, et al.
(author)
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Patients with anaemia can shift from kidney to liver production of erythropoietin as shown by glycoform analysis
- 2013
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In: Journal of Pharmaceutical and Biomedical Analysis. - : Elsevier BV. - 0731-7085 .- 1873-264X. ; 81-82, s. 187-192
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Journal article (peer-reviewed)abstract
- The primary production site of erythropoietin (EPO) is shifted from the liver to the kidney shortly after birth. Under conditions of lost or reduced kidney production, it is valuable to measure the production capacity of the liver. However, there is a lack of urine or serum based methods that can distinguish endogenous EPO produced in different cell types. Here is presented a method based on chromatographic interaction with the lectin wheat germ agglutinin (WGA) that can distinguish presumably liver-produced EPO, found in anaemic patients receiving epoetin and darbepoetin, from kidney-produced EPO found in healthy individuals.All the tested samples from haemodialysis patients with end-stage renal disease showed a presence of liver EPO. In some samples, the liver-produced EPO made up 90–100% of total EPO at a concentration of 8–10 ng/L in urine, which indicates that the liver has a quite high production capacity, although not adequate for the degree of anaemia.This glycoform analysis has made it possible to affirm that some anaemic patients can increase their liver-production of EPO. The use of such a method can give better insight into the regulation of non-renal endogenous EPO production, a potential source of EPO intended to replace administration of exogenous EPO.
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| 6. |
- Lönnberg, Maria, et al.
(author)
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Rapid affinity purification of erythropoietin from biological samples using disposable monoliths
- 2010
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In: Journal of Chromatography A. - : Elsevier BV. - 0021-9673 .- 1873-3778. ; 1217:45, s. 7031-7037
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Journal article (peer-reviewed)abstract
- Identification of post-translational modifications of proteins in biological samples often requires access to preanalytical purification and concentration methods In the purification step high or low molecular weight substances can be removed by size exclusion filters and high abundant proteins can be removed or low abundant proteins can be enriched by specific capturing tools In this paper is described the experience and results obtained with a recently emerged and easy-to-use affinity purification kit for enrichment of the low amounts of EPO found in urine and plasma specimens The kit can be used as a pre-step in the EPO doping control procedure as an alternative to the commonly used ultrafiltration for detecting aberrantly glycosylated isoforms The commercially available affinity purification kit contains small disposable anti-EPO monolith columns (6 mu L volume theta 7 mm length 0 15 mm) together with all required buffers A 24-channel vacuum manifold was used for simultaneous processing of samples The column concentrated EPO from 20 mL urine down to 55 mu L eluate with a concentration factor of 240 times while roughly 997% of non-relevant urine proteins were removed The recoveries of Neorecormon (epoetin beta) and the EPO analogues Aranesp and Mircera applied to buffer were high 76% 67% and 57% respectively The recovery of endogenous EPO from human urine was 65% High recoveries were also obtained when purifying human mouse and equine EPO from serum and human EPO from cerebrospinal fluid Evaluation with the accredited EPO doping control method based on isoelectric focusing (IEF) showed that the affinity purification procedure did not change the isoform distribution for rhEPO Aranesp Mircera or endogenous EPO The kit should be particularly useful for applications in which it is essential to avoid carry-over effects a problem commonly encountered with conventional particle-based affinity columns The encouraging results with EPO propose that similar affinity monoliths with the appropriate antibodies should constitute useful tools for general applications in sample preparation not only for doping control of EPO and other hormones such as growth hormone and insulin but also for the study of post-translational modifications of other low abundance proteins in biological and clinical research and for sample preparation prior to in vitro diagnostics.
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| 7. |
- Lönnberg, Maria, et al.
(author)
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Rapid detection of erythropoiesis-stimulating agents in urine and serum
- 2012
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In: Analytical Biochemistry. - : Elsevier BV. - 0003-2697 .- 1096-0309. ; 420:2, s. 101-114
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Journal article (peer-reviewed)abstract
- A rapid and easy-to-use test kit, EPO WGA MAIIA, which can be used for distinguishing various endogenous human erythropoietins (hEPO) and several recombinant hEPOs and EPO analogues, has been evaluated. The test is based on chromatographic separation of the glycosylated isoforms of EPO using wheat germ agglutinin (WGA), and a sensitive immunoassay utilizing anti-EPO carbon black nanostrings and image scanning for quantification. All the reactions take place along the porous layer of a lateral flow micro-column containing WGA and anti-EPO zones. The presence of molecules resembling hEPO, like Mircera, was detected by the aberrant affinity interaction with the antibody zone on the strip. It was possible to distinguish nine recombinant hEPO expressed in hamster and human cell-lines, and also Aranesp and Mircera, from endogenous urine hEPO. The required amount of EPO in the samples, a few pg, is very low compared to other methods for EPO isoform identification. This EPO isoform determination method opens the possibility to monitor recombinant EPO therapy for clinical research and seems to be a valuable candidate to the arsenal of EPO doping control tests.
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| 9. |
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| 12. |
- Thiblin, Ingemar, et al.
(author)
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Anabolic steroids and cardiovascular risk : A national population-based cohort study
- 2015
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In: Drug And Alcohol Dependence. - : Elsevier BV. - 0376-8716 .- 1879-0046. ; 152, s. 87-92
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Journal article (peer-reviewed)abstract
- Background: Non-therapeutic use of anabolic androgenic steroids (AAS) has been associated with various adverse effects; one of the most serious being direct cardiovascular effects with unknown long-term consequences. Therefore, large studies of the association between AAS and cardiovascular outcomes are warranted. We investigated cardiovascular morbidity and mortality in individuals who tested positive for AAS. Methods and results: Between 2002 and 2009, a total of 2013 men were enrolled in a cohort on the date of their first AAS test. Mortality and morbidity after cohort entry was retrieved from national registries. Of the 2013 individuals, 409(20%) tested positive for MS. These men had twice the cardiovascular morbidity and mortality rate as those with negative tests (adjusted hazard ratio (aHR) 2.0; 95% confidence interval (CI) 1.2-3.3). Compared to the Swedish population, all tested men had an increased risk of premature death from all causes (standardized mortality ratio for MS-positive: 19.3, 95% CI 12.4-30.0; for AAS-negative: 8.3,95% CI 6.1-11.0). Conclusion: Non-therapeutic exposure to MS appears to be an independent risk factor for cardiovascular morbidity and premature death.
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