| 11. |
- Ström, Jakob O., 1983-, et al.
(författare)
-
Effects of high and low 17β-estradiol doses on focal cerebral ischemia : negative results
- 2013
-
Ingår i: Scientific Reports. - London, United Kingdom : Nature Publishing Group. - 2045-2322. ; 3
-
Tidskriftsartikel (refereegranskat)abstract
- The reasons why some animal studies indicate that estrogens increase focal cerebral ischemic damage while others show estrogen-induced neuroprotection has hitherto not been fully elucidated. Recent evidence indicates that discrepancies in hormone administration paradigms, resulting in highly different serum hormone concentrations, may account for the dichotomy. The current study aimed to test this hypothesis. Sixty ovariectomized female rats were randomized into three groups differing in 17β-estradiol regimens, and transient focal cerebral ischemia was subsequently induced. All animals were subjected to a small functional testing battery, and three days after MCAo they were sacrificed for infarct size assessment. Infarct sizes did not differ between groups, however clear discrepancies were seen in body weight and feeding behavior. In comparison to sham-operated animals, ovariectomized rats rapidly increased in body weight, whereas the opposite was seen in rats receiving 17beta-estradiol. The weight gain in the ovariectomized rats was paralleled by an increased food intake.
|
|
| 12. |
- Ström, Jakob O., 1983-, et al.
(författare)
-
Hormesis and female sex hormones
- 2011
-
Ingår i: Pharmaceuticals. - Basel, Switzerland : MDPIAG. - 1424-8247. ; 4:5, s. 726-740
-
Forskningsöversikt (refereegranskat)abstract
- Hormone replacement after menopause has in recent years been the subject of intense scientific debate and public interest and has sparked intense research efforts into the biological effects of estrogens and progestagens. However, there are reasons to believe that the doses used and plasma concentrations produced in a large number of studies casts doubt on important aspects of their validity. The concept of hormesis states that a substance can have diametrically different effects depending on the concentration. Even though estrogens and progestagens have proven prone to this kind of dose-response relation in a multitude of studies, the phenomenon remains clearly underappreciated as exemplified by the fact that it is common practice to only use one hormone dose in animal experiments. If care is not taken to adjust the concentrations of estrogens and progestagens to relevant biological conditions, the significance of the results may be questionable. Our aim is to review examples of female sexual steroids demonstrating bidirectional dose-response relations and to discuss this in the perspective of hormesis. Some examples are highlighted in detail, including the effects on cerebral ischemia, inflammation, cardiovascular diseases and anxiety. Hopefully, better understanding of the hormesis phenomenon may result in improved future designs of studies of female sexual steroids.
|
|
| 13. |
- Ström, Jakob O., 1983-, et al.
(författare)
-
Ovariectomy and 17β-estradiol replacement in rats and mice : a visual demonstration
- 2012
-
Ingår i: Journal of Visualized Experiments. - Cambridge, USA : Journal of Visualized Experiments. - 1940-087X. ; :64
-
Tidskriftsartikel (refereegranskat)abstract
- Estrogens are a family of female sexual hormones with an exceptionally wide spectrum of effects. When rats and mice are used in estrogen research they are commonly ovariectomized in order to ablate the rapidly cycling hormone production, replacing the 17β-estradiol exogenously. There is, however, lack of consensus regarding how the hormone should be administered to obtain physiological serum concentrations. This is crucial since the 17β-estradiol level/administration method profoundly influences the experimental results. We have in a series of studies characterized the different modes of 17β-estradiol administration, finding that subcutaneous silastic capsules and per-oral nut-cream Nutella are superior to commercially available slow-release pellets (produced by the company Innovative Research of America) and daily injections in terms of producing physiological serum concentrations of 17β-estradiol. Amongst the advantages of the nut-cream method, that previously has been used for buprenorphine administration, is that when used for estrogen administration it resembles peroral hormone replacement therapy and is non-invasive. The subcutaneous silastic capsules are convenient and produce the most stable serum concentrations. This video article contains step-by-step demonstrations of ovariectomy and 17β-estradiol hormone replacement by silastic capsules and peroral Nutella in rats and mice, followed by a discussion of important aspects of the administration procedures.
|
|
| 14. |
- Ström, Jakob O., 1983-, et al.
(författare)
-
The female menstrual cycle does not influence testosterone concentrations in male partners
- 2012
-
Ingår i: Journal of Negative Results in BioMedicine. - London, United Kingdom : BioMed Central (BMC). - 1477-5751. ; 11, s. 1-7
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The time of ovulation has since long been believed to be concealed to male heterosexual partners. Recent studies have, however, called for revision of this notion. For example, male testosterone concentrations have been shown to increase in response to olfactory ovulation cues, which could be biologically relevant by increasing sexual drive and aggressiveness. However, this phenomenon has not previously been investigated in real-life human settings. We therefore thought it of interest to test the hypothesis that males' salivary testosterone concentrations are influenced by phases of their female partners' menstrual cycle; expecting a testosterone peak at ovulation.Methods: Thirty young, healthy, heterosexual couples were recruited. During the course of 30-40 days, the women registered menses and ovulation, while the men registered sexual activity, physical exercise, alcohol intake and illness (confounders), and obtained daily saliva samples for testosterone measurements. All data, including the registered confounders, were subjected to multiple regression analysis.Results: In contrast to the hypothesis, the ovulation did not affect the testosterone levels, and the resulting testosterone profile during the menstrual cycle was on the average flat. The specific main hypothesis, that male testosterone levels on the day of ovulation would be higher than day 4 of the cycle, was clearly contradicted by a type II error(β)-analysis (< 14.3% difference in normalized testosterone concentration; β = 0.05).Conclusions: Even though an ovulation-related salivary testosterone peak was observed in individual cases, no significant effect was found on a group level.
|
|
| 15. |
|
|
| 16. |
- Ström, Jakob
(författare)
-
The dose-dependent effects of estrogens on ischemic stroke
- 2012
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Estrogens are a group of female sex hormones that in addition to central roles in reproductive functions also have profound impact on for example brain development, blood vessels, bone tissue, metabolism and the immune system. The dominant endogenous production sites for estrogens in females are the ovaries and adipose tissue, while exogenous sources include combined contraceptive hormone treatments and menopausal hormone therapy. A few decades ago, the observation that females in comparison to men seemed to be protected against cerebral ischemia, and that this benefit was partially lost during menopause, sparked the hypothesis that estrogens protect against stroke. This was later confirmed by epidemiological studies and a large number of experimental animal studies, which motivated extensive clinical trials in which estrogens and/or progestagens were administered with the intent to prevent degenerative conditions rather than to ameliorate menopausal symptoms. However, the results were generally disappointing. The largest study, the Women’s Health Initiative (WHI), was discontinued due to the observation of an increased risk of breast cancer, cardiovascular disease and stroke. In parallel, a small number of animal studies in which estrogens were shown to increase damage from cerebral ischemia were published, one of these originating from our laboratory. This was, despite the WHI outcome, a surprising result, since the vast majority of previous animal studies had demonstrated protective effects.Therefore, in an attempt to explain the discordant results, Paper 1, and later Paper 4, of the current thesis were planned, in which four 17β-estradiol administration methods were tested. Substantial differences in serum hormone concentrations resulted from the different methods. Most importantly, the commercially available slow-release pellets used in our earlier experiments resulted in extremely high serum concentrations of 17β-estradiol. In Paper 2, 66 published studies that had investigated the effects of estrogens on stroke were meta-analyzed to pin-point the methodological reasons for the result dichotomy. Strikingly, in all six studies in which estrogens had produced damaging effects, the same type of slow-release pellets had been used, although these were used in a minority of the total number of studies. Paper 3 substantially strengthened the hypothesis that administration methods were crucial by showing that repeating the earlier experiment from our laboratory in which pellets had been used, but using a low-dose regimen instead, switched the estrogen effects from neurodamaging to neuroprotective. In Paper 5, an effort was made to challenge the assumption that the dose, and not the administration method per se, was the key factor, however this failed due to large intra-group infarct size variability.The current thesis adds evidence to the notion that differences in administration methods and their resulting serum concentrations of 17β-estradiol constitute a major factor responsible for the dichotomous results in studies investigating estrogens’ effects on cerebral ischemia. Even though results from animal studies are difficult to extrapolate to humans, this has a bearing on the menopausal hormone therapy debate, indicating that the risk of stroke could be reduced if serum concentrations of estrogens are minimized.
|
|
| 17. |
- Amatya, B, et al.
(författare)
-
Expression of tachykinins and their receptors in plaque psoriasis with pruritus
- 2011
-
Ingår i: BRITISH JOURNAL OF DERMATOLOGY. - : Blackwell Publishing Ltd. - 0007-0963 .- 1365-2133. ; 164:5, s. 1023-1029
-
Tidskriftsartikel (refereegranskat)abstract
- Pandgt;Background Cutaneous melanoma is rapidly increasing in incidence worldwide and approximately 5% of melanomas are hereditary. Deletions in chromosome 1p36 have been detected in melanoma but no candidate melanoma tumour suppressor gene has yet been found in this area. Recently, strong evidence has been reported that CHD5 is a tumour suppressor gene in this region. Objectives To investigate CHD5 involvement in familial melanoma. Methods Peripheral blood DNA from 47 melanoma families who do not carry mutations in any of the three currently recognized melanoma genes, 398 patients with sporadic melanoma and 398 geographically matched nonmelanoma-bearing controls were studied. Linkage investigation, single nucleotide polymorphism (SNP) genotyping and mutation screening studies were carried out on the CHD5 locus. Results The CHD5 gene was not excluded by linkage analysis in any of the families. On SNP genotyping, the CHD5 rs7513548 SNP was found to be significantly associated with sporadic melanoma (odds ratio 1 center dot 53, 95% confidence interval 1 center dot 13-2 center dot 06). The AG genotype was found in 208 cases and 169 controls (cf. 141 and 175 cases and controls, respectively, for the AA genotype). On CHD5 mutation screening, a total of 50 single-base substitutions were detected. Of these, 39 were intronic and 11 were exonic. While 32 were previously recognized variants, 18 were newly identified. Three, in exons 4, 31 and 32, led to nonsynonymous substitutions. A p.Met1576Ile substitution was identified in a mother and daughter, both with invasive cutaneous melanoma. Conclusions This study appears to be the first report of CHD5 variants in familial cutaneous melanoma. Such CHD5 variants could block or alter the ability of CHD5 to regulate the cell cycle pathway and to effect cellular control. As only one of the 47 families studied has this variant, it appears to be a rare event and further screening of melanoma families is required to confirm whether or not CHD5 is involved in melanoma pathogenesis.
|
|
| 18. |
|
|
| 19. |
- Brynhildsen, Jan, et al.
(författare)
-
Leptin and adiponectin in cord blood from children of normal weight, overweight and obese mothers
- 2013
-
Ingår i: Acta Paediatrica. - : Wiley-Blackwell. - 0803-5253 .- 1651-2227. ; 102:6, s. 620-624
-
Tidskriftsartikel (refereegranskat)abstract
- Aim To study cord blood concentrations of adiponectin and leptin in children born by normal weight, overweight and obese mothers and to study these parameters in relation to a weight gain intervention programme for obese mothers. Methods Ten millilitre cord blood was collected and analysed for leptin and adiponectin concentrations in children with gestational age andgt;37weeks born by 60 normal weight, 45 overweight and 145 obese mothers. 82 obese mothers took part in a weight gain intervention programme. Results Concentrations of leptin and adiponectin were higher in cord blood from children of overweight and obese mothers compared with children of normal weight mothers (leptin: Md 13.2, 30, 3 and 90.2ng/mL respectively, pandlt;0.001; adiponectin 35.9, 205.4, 213.8ng/L pandlt;0.001). No differences were found between overweight and obese mothers. The weight gain intervention programme for obese pregnant women had significant effects on the weight gain during pregnancy but had no effects on cord blood serum concentrations of leptin and adiponectin. Conclusion Cord blood leptin and adiponectin concentrations were higher in children born by overweight or obese women compared with children of normal weight mothers. A weight gain intervention programme for obese pregnant women did not affect these results. Intrauterine exposition to high concentrations of leptin and adiponectin may play a role in weight development later in life.
|
|
| 20. |
- Carlson, Joyce, et al.
(författare)
-
Digestionsorganens sjukdomar
- 2012. - 9
-
Ingår i: Laurells Klinisk kemi i praktisk medicin. - Lund. - 9789144047874 ; , s. 441-496
-
Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Klinisk kemi i praktisk medicin används som kurslitteratur för läkare, biomedicinska analytiker och biomedicinare sedan 40 år tillbaka. Den finns på avdelningar, mottagningar och vårdcentraler - överallt där man behöver ta prover för kliniskt kemiska analyser och tolka deras resultat. Nu föreligger den i sin nionde upplaga efter omfattande revision och med nyskrivna kapitel. I denna upplaga har innehållet organiserats med tydlig anknytning till kliniska problemområden. Alla kapitel har grundligt reviderats. Avsnitten om tolkning av analysresultat, allergi och autoimmunitet, hjärtinfarkt och hjärtskademarkörer, digestionsorganens sjukdomar, graviditet, infertilitet och prenataldiagnostik samt läkemedel, förgiftningar och missbruk är helt nyskrivna. Boken kan användas både för att slå upp fakta om specifika analyser och för att förstå de sjukdomsmekanismer som är av betydelse för tolkningen av laboratorieresultat. Modern medicinsk praxis är patientcentrerad och har sitt fundament i ett nära samspel mellan klinik, laboratorier och patienter. Kunskapsfragment inom klinisk kemi är lättillgängliga för alla och envar på nätet, men ger sällan den helhetsbild som behövs för grundlig förståelse och därmed optimal användning av laboratorieanalyser. Denna bok ger sådan helhetsbild.
|
|
