| 1. |
- David, Fresnais, et al.
(författare)
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Lack of association in acne and salivary testosterone
- 2018
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Ingår i: Journal of controversies in biomedical research. - : Codon Publications. - 2205-5975. ; 4:1
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Tidskriftsartikel (refereegranskat)abstract
- The pathogenesis of acne vulgaris has only been partially elucidated. Various hormones, especially androgens, are likely to play a role, but results of studies are still inconclusive. The objective of the current study was to investigate whether day to day variation in salivary testosterone correlates with acne in males. Saliva samples were collected for 120 consecutive days from each of the 40 males. Salivary testosterone concentrations were measured by enzyme-linked immunosorbent assay (ELISA). Facial acne lesions were assessed on a daily basis by photography by the participating males. Potential confounders’ (sexual intercourse, masturbation, physical exercise and disease) were also registered every day by the participants. A significant but weak association between salivary testosterone and acne was found (n = 4602, r = 0.031, P = 0.034). Elevated testosterone concentrations were associated with an increase in acne, but when testosterone concentrations were above twice the individual average, acne lesions paradoxically decreased. The current results indicate that daily fluctuations in salivary testosterone levels in males are associated with acne patterns, but the weak correlation suggests that the effect is too small to be of clinical significance. The analysis in the current study was complicated by a large number of days on which the participants had no acne, as well as the seemingly non-monotonic relation between testosterone and acne. This may indicate that the actual relation is stronger than concluded here.
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| 2. |
- Ingberg, Edvin, 1988-, et al.
(författare)
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16S metagenomics for bacterial identification versus cultures in acute pharyngotonsillitis patients and controls
- 2018
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Konferensbidrag (refereegranskat)abstract
- Background: Sore throat/pharyngotonsillitis is a very common condition. While most cases are viral, the primary bacterial pathogen is group A beta-hemolytic streptococcus (Streptococcus pyogenes). Further, Fusobacterium necrophorum has over the last decade attracted attention. rnrnSequence-based techniques continue to gain ground in medical microbiology. To describe the microbiota in a sample, either the whole genomes (metagenomics) or marker genes/genomic regions (metataxonomics), such as the 16S rRNA gene, can be sequenced. Some studies have investigated how findings from these methods correspond to conventional microbiological methods for infectious diseases, such as cultures. However, no previous study has approached the condition acute pharyngotonsillitis this way.Methods: Throat samples from patients with acute sore throat (n=129) and controls (n=86), both groups aged 15-45, were collected. DNA was extracted and the V3-V4 regions of the 16S rRNA genes were amplified using PCR. After normalization based on fragment analysis, and size selection with Ampure beads and PCR against adapter sequences coupled to the V3-V4 fragments, clonal amplifiction was performed with isothermal PCR. Finally, sequencing was performed on the Ion Torrent S5 XL. The SILVA database was used for taxonomic classification and the results were compared to culture findings for S. pyogenes and F. necrophorum, using Mann Whitney U tests.Results: Among the 215 samples, 46 patients and 1 of the controls were culture-positive for S. pyogenes. For F. necrophorum, 20 patients and 3 controls were culture-positive. Seven of the samples were culture-positive for both S. pyogenes and F. necrophorum. rnrnIn the metataxonomic analysis, S. pyogenes were significantly more abundant among patients than controls (p=0.0046), and in samples culture-positive for S. pyogenes, compared to culture-negative (p<0.0001).The percent of reads representing F. necrophorum were significantly higher in patients compared to controls (p<0.001), as well as in culture-positive samples compared to culture-negative (p<0.0001). rnrnAlthough significant differences between culture-positive and culture-negative samples were seen, even among culture-positive samples the abundance of S. pyogenes or F. necrophorum were on average low (2,1% and 10,6%, respectively) and with large variation (0-49,8% and 0-76,1%, respectively).Conclusions: Findings from a metataxonomic 16S rRNA gene analysis differed regarding species of interest between groups based on symptoms of a sore throat or culture findings. However, the results were heterogeneous and difficult to interpret for a single sample.
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| 3. |
- Ingberg, Edvin, 1988-
(författare)
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Challenges in experimental stroke research : The 17β-estradiol example
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Ischemic stroke causes millions of deaths around the world each year, and surviving patients often suffer from long-term disability. Hundreds of promising drug candidates have been identified in animal models, but the clinical trials have repeatedly failed. Lack of methodological quality in the animal studies, e.g. low statistical power as a result of small group sizes in combination with high outcome variability and high mortality, has been suggested to in part explain the lack of translational success. In the meta-analytical Papers II and Paper V, we therefore investigated how method parameters impact infarct size variation and mortality in rodent stroke studies. These findings can help researchers to optimize their animal models or to more exactly predict variability and mortality given a certain experimental setup.The relation between ischemic stroke and estrogens is complex. Premenopausal women have a lower risk of stroke than men of the same age, suggesting that female sex hormones provide protection against cerebrovascular events. The idea of a beneficial effect on the brain of estrogens was also supported by epidemiological studies showing that estrogens given as postmenopausal hormone replacement therapy decreased the risk of stroke. However, subsequent clinical trials reported the opposite, an increased risk. Interestingly, discrepancies exist also in the animal stroke literature. The majority of the rodent studies on the effects of estrogens have shown protection, but there are also several examples of increased damage. Based on experimental results and a meta-analysis, it was hypothesized that differences in hormone administration methods and their resulting plasma concentrations of estrogens might explain the previous discordant animal findings. Paper I investigated the commonly used methods for 17β-estradiol administration and found that the popular slow-release pellets produced high and unpredictable serum concentrations. A novel method with 17β-estradiol administered orally in Nutella® was also evaluated with promising results. Paper III extracted data regarding methodological choices from all previously published estrogen-stroke studies, and showed through metaanalysis that slow-release pellets are more prone to render estrogens damaging. Finally, Paper IV tested whether estrogens could both exert neuroprotection and promote detrimental effects merely depending on dose and irrespective of the administration route. Surprisingly, and in contrast to the hypothesis, a significant negative correlation was found between 17β-estradiol dose group and infarct size meaning that the higher the dose, the smaller the infarcts.In summary, this thesis does not confirm the hypothesis of dose-related neuroprotective vs neurodamaging effects of estrogens on ischemic stroke. If high estrogen doses/plasma concentrations per se can cause increased stroke damage, such a phenomenon is not very robust, and seems to depend on tight dose ranges and/or other experimental circumstances. Although not directly applicable to the clinical situation, hopefully in a long-term perspective these findings may contribute in elucidating when estrogens are beneficial and when they are harmful. Further, it adds to the growing literature on how the quality of experimental stroke research can be increased to try to overcome translational difficulties.
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| 4. |
- Ingberg, Edvin, 1988-, et al.
(författare)
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Effect of laser Doppler flowmetry and occlusion time on outcome variability and mortality in rat middle cerebral artery occlusion : inconclusive results
- 2018
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Ingår i: BMC Neuroscience. - London : BioMed Central. - 1471-2202. ; 19:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Stroke is among the leading causes of death and disability. Although intense research efforts have provided promising treatment options in animals, most clinical trials in humans have failed and the therapeutic options are few. Several factors have been suggested to explain this translational difficulty, particularly concerning methodology and study design. Consistent infarcts and low mortality might be desirable in some, but not all, studies. Here, we aimed to investigate whether the use of laser Doppler flowmetry (LDF) and the occlusion time (60 vs. 45 min) affected outcome variability and mortality in a rat stroke model. Eighty ovariectomized female Wistar rats were subjected to ischemic stroke using intraluminal filament middle cerebral artery occlusion with or without LDF and with occlusion times of 45 or 60 min. Outcome was evaluated by triphenyl tetrazolium chloride staining of brain slices to measure infarct size and a modified sticky tape test.RESULTS: Neither LDF nor occlusion times of 45 versus 60 min significantly affected mortality, outcome variability or outcome severity.CONCLUSIONS: Due to the unexpectedly high mortality and variability the statistical power was very low and thus the results were inconclusive.
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| 5. |
- Ingberg, Edvin, 1988-, et al.
(författare)
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Effects of high and low 17β-estradiol doses on focal cerebral ischemia in rats
- 2016
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Ingår i: Scientific Reports. - London, United Kingdom : Nature Publishing Group. - 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- The majority of the numerous animal studies of the effects of estrogens on cerebral ischemia have reported neuroprotective results, but a few have shown increased damage. Differences in hormone administration methods, resulting in highly different 17β-estradiol levels, may explain the discrepancies in previously reported effects. The objective of the present study was to test the hypothesis that it is the delivered dose per se, and not the route and method of administration, that determines the effect, and that high doses are damaging while lower doses are protective. One hundred and twenty ovariectomized female Wistar rats (n = 40 per group) were randomized into three groups, subcutaneously administered different doses of 17β-estradiol and subjected to transient middle cerebral artery occlusion. The modified sticky tape test was performed after 24 h and the rats were subsequently sacrificed for infarct size measurements. In contrast to our hypothesis, a significant negative correlation between 17β-estradiol dose and infarct size was found (p = 0.018). Thus, no support was found for the hypothesis that 17β-estradiol can be both neuroprotective and neurotoxic merely depending on dose. In fact, on the contrary, the findings indicate that the higher the dose of 17β-estradiol, the smaller the infarct.
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| 6. |
- Ingberg, Edvin, 1988-, et al.
(författare)
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Elevated body swing test after focal cerebral ischemia in rodents : methodological considerations
- 2015
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Ingår i: BMC Neuroscience. - : Springer Science and Business Media LLC. - 1471-2202. ; 16
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Tidskriftsartikel (refereegranskat)abstract
- Background: The elevated body swing test (EBST) is a behavioral test used to evaluate experimental stroke in rodents. The basic idea is that when the animal is suspended vertically by the tail, it will swing its head laterally to the left or right depending on lesion side. In a previous study from our lab using the EBST after middle cerebral artery occlusion (MCAo), rats swung contralateral to the infarct day 1 post-MCAo, but ipsilateral day 3 post-MCAo. This shift was unexpected and prompted us to perform the present study. First, the literature was systematically reviewed to elucidate whether a similar shift had been noticed before, and if consensus existed regarding swing direction. Secondly, an experiment was conducted to systematically investigate the suggested behavior. Eighty-three adult male and female Sprague-Dawley rats were subjected to MCAo or sham surgery and the EBST was performed up to 7 days after the lesion.Results: Both experimentally and through systematic literature review, the present study shows that the direction of biased swing activity in the EBST for rodents after cerebral ischemia can differ and even shift over time in some situations. The EBST curve for females was significantly different from that of males after the same occlusion time (p = 0.023).Conclusions: This study highlights the importance of adequate reporting of behavioral tests for lateralization and it is concluded that the EBST cannot be recommended as a test for motor asymmetry after MCAo in rats.
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| 7. |
- Ingberg, Edvin, 1988-, et al.
(författare)
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Method parameters' impact on mortality and variability in mouse stroke experiments : a meta-analysis
- 2016
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Ingår i: Scientific Reports. - London, England : Nature Publishing Group. - 2045-2322. ; 11:SUPP 3, s. 108-108
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Tidskriftsartikel (refereegranskat)abstract
- Although hundreds of promising substances have been tested in clinical trials, thrombolysis currently remains the only specific pharmacological treatment for ischemic stroke. Poor quality, e.g. low statistical power, in the preclinical studies has been suggested to play an important role in these failures. Therefore, it would be attractive to use animal models optimized to minimize unnecessary mortality and outcome variability, or at least to be able to power studies more exactly by predicting variability and mortality given a certain experimental setup. The possible combinations of methodological parameters are innumerous, and an experimental comparison of them all is therefore not feasible. As an alternative approach, we extracted data from 334 experimental mouse stroke articles and, using a hypothesis-driven meta-analysis, investigated the method parameters' impact on infarct size variability and mortality. The use of Swiss and C57BL6 mice as well as permanent occlusion of the middle cerebral artery rendered the lowest variability of the infarct size while the emboli methods increased variability. The use of Swiss mice increased mortality. Our study offers guidance for researchers striving to optimize mouse stroke models.
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| 8. |
- Ström, Jakob O., 1983-, et al.
(författare)
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Male Testosterone Does Not Adapt to the Partner's Menstrual Cycle
- 2018
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Ingår i: Journal of Sexual Medicine. - : Elsevier. - 1743-6095 .- 1743-6109. ; 15:8, s. 1103-1110
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Tidskriftsartikel (refereegranskat)abstract
- Background: It has not yet been established whether men in heterosexual relationships adapt their hormone levels to their female partner's menstrual cycle to allocate reproductive resources to the period when the female is actually fertile.Aim: This prospective observational study tested the hypothesis that some males have peaks in testosterone or acne (a possible biomarker for androgen activity) near their partners' ovulation, whereas other males display the opposite pattern.Methods: 48 couples supplied menstrual cycle data, male salivary samples, and a protocol of daily activities for 120 days. Daily saliva samples were analyzed for testosterone concentrations by enzyme-linked immunosorbent assay. The main hypothesis was tested by analyzing whether each individual male's testosterone/acne response to ovulation (either an increase or a decrease in comparison to the individual's average levels) was stable over time. To do this, we analyzed the Spearman correlation between individually normalized periovulatory testosterone and acne during the first half of the study versus the second half of the study.Outcomes: Correlation between each male individual's periovulatory testosterone and acne patterns during the first half of the study versus the second half of the study.Results: No predictability in the male individuals' testosterone (Spearman's rho = -0.018, P = .905) or acne (Spearman's rho = -0.036, P = .862) levels during ovulation was found.Clinical translation: The study being "negative," there is no obvious translational potential in the results.Strengths and limitations: The main strength of this study lies in the excellent compliance of the study participants and the large number of sampling timepoints over several menstrual cycles, thereby allowing each male individual to be his own control subject. A limitation is that samples were only obtained in the morning; however, including later timepoints would have introduced a number of confounders and would also have hampered the study's feasibility.Conclusions: The current results strongly indicate that male morning testosterone levels neither increase nor decrease in response to the partner's ovulation. This discordance to previous laboratory studies could indicate either that (i) the phenomenon of hormonal adaptation of men to women does not exist and earlier experimental studies should be questioned, (ii) that the phenomenon is short-lived/acute and wanes if the exposure is sustained, or (iii) that the male testosterone response may be directed toward other women than the partner. Copyright (C) 2018, The Authors. Published by Elsevier Inc. on behalf of the International Society for Sexual Medicine.
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