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| 2. |
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| 3. |
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| 4. |
- Brunström, Mattias, et al.
(författare)
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From efficacy in trials to effectiveness in clinical practice : The Swedish Stroke Prevention Study
- 2016
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Ingår i: Blood Pressure. - : Informa UK Limited. - 0803-7051 .- 1651-1999. ; 25:4, s. 206-211
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Tidskriftsartikel (refereegranskat)abstract
- Blood pressure treatment has shown great efficacy in reducing cardiovascular events in randomized controlled trials. If this is effective in reducing cardiovascular disease in the general population, is less studied. Between 2001 and 2009 we performed an intervention to improve blood pressure control in the county of Vasterbotten, using Sodermanland County as a control. The intervention was directed towards primary care physicians and included lectures on blood pressure treatment, a computerized decision support system with treatment recommendations, and yearly feed back on hypertension control. Each county had approximately 255000 inhabitants. Differences in age and incidence of cardiovascular disease were small. During follow-up, more than 400000 patients had their blood pressure recorded. The mean number of measurements was eight per patient, yielding a total of 3.4 million blood pressure recordings. The effect of the intervention will be estimated combining the blood pressure data collected from the electronic medical records, with data on stroke, myocardial infarction and mortality from Swedish health registers. Additional variables, from health registers and Statistics Sweden, will be collected to address for confounders. The blood pressure data collected within this study will be an important asset for future epidemiological studies within the field of hypertension.
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| 5. |
- Cardinale, Daniele A., 1982-, et al.
(författare)
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Influence of Hyperoxic-Supplemented High-Intensity Interval Training on Hemotological and Muscle Mitochondrial Adaptations in Trained Cyclists.
- 2019
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Ingår i: Frontiers in Physiology. - : Frontiers Media S.A.. - 1664-042X. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Background: Hyperoxia (HYPER) increases O2 carrying capacity resulting in a higher O2 delivery to the working muscles during exercise. Several lines of evidence indicate that lactate metabolism, power output, and endurance are improved by HYPER compared to normoxia (NORM). Since HYPER enables a higher exercise power output compared to NORM and considering the O2 delivery limitation at exercise intensities near to maximum, we hypothesized that hyperoxic-supplemented high-intensity interval training (HIIT) would upregulate muscle mitochondrial oxidative capacity and enhance endurance cycling performance compared to training in normoxia. Methods: 23 trained cyclists, age 35.3 ± 6.4 years, body mass 75.2 ± 9.6 kg, height 179.8 ± 7.9 m, and VO2max 4.5 ± 0.7 L min-1 performed 6 weeks polarized and periodized endurance training on a cycle ergometer consisting of supervised HIIT sessions 3 days/week and additional low-intensity training 2 days/week. Participants were randomly assigned to either HYPER (FIO2 0.30; n = 12) or NORM (FIO2 0.21; n = 11) breathing condition during HIIT. Mitochondrial respiration in permeabilized fibers and isolated mitochondria together with maximal and submaximal VO2, hematological parameters, and self-paced endurance cycling performance were tested pre- and posttraining intervention. Results: Hyperoxic training led to a small, non-significant change in performance compared to normoxic training (HYPER 6.0 ± 3.7%, NORM 2.4 ± 5.0%; p = 0.073, ES = 0.32). This small, beneficial effect on the self-paced endurance cycling performance was not explained by the change in VO2max (HYPER 1.1 ± 3.8%, NORM 0.0 ± 3.7%; p = 0.55, ES = 0.08), blood volume and hemoglobin mass, mitochondrial oxidative phosphorylation capacity (permeabilized fibers: HYPER 27.3 ± 46.0%, NORM 16.5 ± 49.1%; p = 0.37, ES = 3.24 and in isolated mitochondria: HYPER 26.1 ± 80.1%, NORM 15.9 ± 73.3%; p = 0.66, ES = 0.51), or markers of mitochondrial content which were similar between groups post intervention. Conclusions: This study showed that 6 weeks hyperoxic-supplemented HIIT led to marginal gain in cycle performance in already trained cyclists without change in VO2max, blood volume, hemoglobin mass, mitochondrial oxidative phosphorylation capacity, or exercise efficiency. The underlying mechanisms for the potentially meaningful performance effects of hyperoxia training remain unexplained and may raise ethical questions for elite sport.
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| 6. |
- Demker, Marie, 1960, et al.
(författare)
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Förfinar arbetet mot rasism
- 2015
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Ingår i: Göteborgs-Posten. - 1103-9345. ; :17 juni 2015
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Tidskriftsartikel (populärvet., debatt m.m.)
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| 7. |
- Fernandez, Celine, et al.
(författare)
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Disturbed cholesterol homeostasis in hormone-sensitive lipase-null mice.
- 2008
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Ingår i: American journal of physiology. Endocrinology and metabolism. - : American Physiological Society. - 0193-1849 .- 1522-1555. ; 295:4
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Tidskriftsartikel (refereegranskat)abstract
- Transcriptomics analysis revealed that genes involved in hepatic de novo cholesterol synthesis were downregulated in fed HSL-null mice that had been on a high-fat diet (HFD) for 6 mo. This finding prompted a further analysis of cholesterol metabolism in HSL-null mice, which was performed in fed and 16-h-fasted mice on a normal chow diet (ND) or HFD regimen. Plasma cholesterol was elevated in HSL-null mice, in all tested conditions, as a result of cholesterol enrichment of HDL and VLDL. Hepatic esterified cholesterol content and ATP-binding cassette transporter A1 (ABCA1) mRNA and protein levels were increased in HSL-null mice regardless of the dietary regimen. Unsaturated fatty acid composition of hepatic triglycerides was modified in fasted HSL-null mice on ND and HFD. The increased ABCA1 expression had no major effect on cholesterol efflux from HSL-null mouse hepatocytes. Taken together, the results of this study suggest that HSL plays a critical role in the hydrolysis of cytosolic cholesteryl esters and that increased levels of hepatic cholesteryl esters, due to lack of action of HSL in the liver, are the main mechanism underlying the imbalance in cholesterol metabolism in HSL-null mice.
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| 8. |
- Gaulton, Kyle J, et al.
(författare)
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Genetic fine mapping and genomic annotation defines causal mechanisms at type 2 diabetes susceptibility loci.
- 2015
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 47:12, s. 1415-1415
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Tidskriftsartikel (refereegranskat)abstract
- We performed fine mapping of 39 established type 2 diabetes (T2D) loci in 27,206 cases and 57,574 controls of European ancestry. We identified 49 distinct association signals at these loci, including five mapping in or near KCNQ1. 'Credible sets' of the variants most likely to drive each distinct signal mapped predominantly to noncoding sequence, implying that association with T2D is mediated through gene regulation. Credible set variants were enriched for overlap with FOXA2 chromatin immunoprecipitation binding sites in human islet and liver cells, including at MTNR1B, where fine mapping implicated rs10830963 as driving T2D association. We confirmed that the T2D risk allele for this SNP increases FOXA2-bound enhancer activity in islet- and liver-derived cells. We observed allele-specific differences in NEUROD1 binding in islet-derived cells, consistent with evidence that the T2D risk allele increases islet MTNR1B expression. Our study demonstrates how integration of genetic and genomic information can define molecular mechanisms through which variants underlying association signals exert their effects on disease.
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| 9. |
- Kulka, Ulrike, et al.
(författare)
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RENEB - Running the European Network of biological dosimetry and physical retrospective dosimetry
- 2017
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Ingår i: International Journal of Radiation Biology. - : Informa UK Limited. - 0955-3002 .- 1362-3095. ; 93:1, s. 2-14
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: A European network was initiated in 2012 by 23 partners from 16 European countries with the aim to significantly increase individualized dose reconstruction in case of large-scale radiological emergency scenarios. Results: The network was built on three complementary pillars: (1) an operational basis with seven biological and physical dosimetric assays in ready-to-use mode, (2) a basis for education, training and quality assurance, and (3) a basis for further network development regarding new techniques and members. Techniques for individual dose estimation based on biological samples and/or inert personalized devices as mobile phones or smart phones were optimized to support rapid categorization of many potential victims according to the received dose to the blood or personal devices. Communication and cross-border collaboration were also standardized. To assure long-term sustainability of the network, cooperation with national and international emergency preparedness organizations was initiated and links to radiation protection and research platforms have been developed. A legal framework, based on a Memorandum of Understanding, was established and signed by 27 organizations by the end of 2015. Conclusions: RENEB is a European Network of biological and physical-retrospective dosimetry, with the capacity and capability to perform large-scale rapid individualized dose estimation. Specialized to handle large numbers of samples, RENEB is able to contribute to radiological emergency preparedness and wider large-scale research projects.
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| 10. |
- Lindberg, Marie K, 1975, et al.
(författare)
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Estrogen receptor specificity for the effects of estrogen in ovariectomized mice.
- 2002
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Ingår i: The Journal of endocrinology. - : Bioscientifica. - 0022-0795 .- 1479-6805. ; 174:2, s. 167-78
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Tidskriftsartikel (refereegranskat)abstract
- Estrogen exerts a variety of important physiological effects, which have been suggested to be mediated via the two known estrogen receptors (ERs), alpha and beta. Three-month-old ovariectomized mice, lacking one or both of the two estrogen receptors, were given estrogen subcutaneously (2.3 micro g/mouse per day) and the effects on different estrogen-responsive parameters, including skeletal effects, were studied. We found that estrogen increased the cortical bone dimensions in both wild-type (WT) and double ER knockout (DERKO) mice. DNA microarray analysis was performed to characterize this effect on cortical bone and it identified four genes that were regulated by estrogen in both WT and DERKO mice. The effect of estrogen on cortical bone in DERKO mice might either be due to remaining ERalpha activity or represent an ERalpha/ERbeta-independent effect. Other effects of estrogen, such as increased trabecular bone mineral density, thymic atrophy, fat reduction and increased uterine weight, were mainly ERalpha mediated.
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| 11. |
- Lindholm, Maria, et al.
(författare)
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Slutrapport Sendsmart
- 2014
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Rapport (övrigt vetenskapligt/konstnärligt)
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| 12. |
- Lindholm, Maria, et al.
(författare)
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Slutrapport Sendsmart
- 2014
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Sverige är ett av de länder som har störst inflyttning till städer i Europa. Denna ökande urbanisering leder också till ökade transportbehov i städer, för både personer och gods. För att kunna uppnå hållbarhet i transportsystemet, fordras lösningar som utgår från en övergripande systemsyn där hela kedjan med transporter inom staden integreras, både lokal- och fjärrtransporter men även innovativa lösningar i respektive del. Godsprojektet Sendsmart har genomförts i Göteborg mellan september 2012 och september 2014. Nitton partners har varit delaktiga i totalt fem arbetspaket. Projektet har letts av Closer på Lindholmen Science Park AB och har fokuserat på transporter inom tre områden som tillsammans genererar majoriteten av transportarbetet i urbana områden: Godsförsörjning, Bygg- och anläggning samt Avfall och återvinning. Dessa tre områden har kompletterats med arbetspaket för Utvärdering respektive Visualisering. Målet med Sendsmart har varit att utveckla, testa och demonstrera innovativa tjänster och system med internationell framgång för hållbara godstransporter i storstadsområden. Inom samtliga tre delprojekt har det gjorts dels utredningar kring lämpliga projekt, dels genomförts demonstrationsprojekt som fått såväl nationell som internationell uppmärksamhet. Mikroterminalen på Lindholmen – Lindholmsleveransen – har under projektet vidareutvecklats och mikroterminalen i innerstaden – Stadsleveransen – har under projektet startats upp, båda med små eldrivna fordon kompletterat med lastcykel, med resultat i förbättrad transporteffektivitet inom dessa områden. För byggtransporter har ett system kallat ”Massabyte” testats och driftsatts med gott resultat, men ännu ej fullkomligt kommersiellt, vilket kan komma att ta tid. Undersökning om alternativa transportsätt för massor med pråm har utretts och pråmen har konstaterats effektiv vid rätt förutsättningar. För avfallshanteringen har tidig hämtning testats och det har konstaterats att fordonet ej är den mest störande ljudkällan, utan kärl- och kringutrustning. Genom ett antal åtgärder, bl.a. dämpade kärl, har ett gott resultat uppnåtts och de boende har ej störts av fältprovet. Chaufförer förespråkar avfallshantering på tidiga morgontimmar efter försöket, med hänsyn till en mycket bättre arbetsmiljö. De övergripande målen med Sendsmart är uppfyllda med goda resultat. De främsta erfarenheterna från projektet rör vikten av dialog och samverkan med olika intressenter. Projektets exakta utformning var ej given från början och det har visat sig framgångsrikt – men svårt och tidskrävande – att tillsammans med intressenter identifiera olika möjliga lösningar till specifika problem och sedan med långsiktighet i fokus konceptualisera och implementera lösningar i små steg. Att processen är tidskrävande måste dock understrykas tillsammans med att personkemi, politik och affärsstrategier har stor inverkan på hur man kan och vill samarbeta.
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| 13. |
- Lindholm, Sara
(författare)
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Neurochemical and behavioral studies on ethanol and brain opiod interactions in the brain
- 2001
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Substance dependence is a devastating disorder that produces enormous socio-economic costs, personal tragedies and health related problems. The brain mesolimbic dopamine pathway originating in the ventral tegmental area (VTA) with projections to limbic brain structures such as the nucleus accumbens has been implicated in the reinforcing effects of different drugs of abuse. The basal and drug-induced activity of mesolimbic dopamine neurons is modulated by endogenous opioids. Non-selective opioid receptor antagonists are increasingly used in the treatment of alcohol dependence, and ligands selective for the different opioid receptor types have recently been suggested to be effective in the treatment of cocaine and heroin addiction in humans. The present thesis examined the neurobiological and behavioral interactions between ethanol and endogenous opioids, with specific focus on the dynorphin/kappa-opioid receptor system. In addition, the effects of concurrent ethanol and cocaine administration on kappa-opioid receptor mRNA and dopamine transmission in the mesolimbic pathway were studied. Repeated ethanol administration significantly increased the dynorphin B levels in the nucleus accumbens at 30 min and at 21 days after the last dose. The kappa-receptor mRNA levels were significantly reduced in both the VTA and the nucleus accumbens after separate as well as concurrent administration of ethanol and cocaine. These results suggest that repeated exposure to ethanol may lead to neuroadaptive changes in the dynorphin/kappa-receptor system associated with the mesolimbic pathway, some of which may be long lasting. Following repeated ethanol administration, extracellular dopamine concentrations in the nucleus accumbens were significantly increased in rats pre-treated with ethanol, but not in the controls. Conversely, the inibitory effect of the kappa-receptor agonist U50,488H on dopamine levels was more pronounced in saline- than in ethanol -pre-treated rats. This suggests that repeated ethanol changes the sensitivity of the dynorphin/kappa-receptor system, and/or enhances the activity of the endogenous agonist dynorphin. Pre-treatment with ethanol increased the effect of cocaine on dopamine levels in the nucleus accumbens. Cocaine-induced stereotypic behavior was unaffected by ethanol pre-treatment. The enhanced dopamine release in the nucleus accumbens may be related to the heightened experience produced by concurrent intake of ethanol and cocaine in humans, and could influence the probability of co- abuse. Naltrexone and the selective delta-receptor antagonists ICI-174,864 and naltrindole significantly decreased voluntary ethanol intake, whereas the mu1-antagonist naloxonazine had no significant effect. The kappa-receptor agonist U50,488H decreased ethanol intake, whereas the kappa-receptor antagonist nor-BNI lacked effect by itself, but reduced the effect of U50,488H. This suggests that not only the mu-/delta-receptor systems, but also the kappa-receptor systems modulate volitional ethanol intake in the rat. In summary, repeated exposure to ethanol andlor cocaine produces alterations in the brain dynorphin/kappa-opioid receptor system. Further, voluntary ethanol intake is reduced by selective opioid receptor ligands. It is suggested that the dynorphinergic system is involved in the pathophysiology of alcohol dependence, and may represent a potential pharinacotherapeutic target in the treatment of this disorder.
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| 14. |
- Lindholm, Sara, et al.
(författare)
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Nociceptin/orphanin FQ tissue concentration in the rat brain : Effects of repeated ethanol administration at various post-treatment intervals
- 2002
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Ingår i: Progress in Neuro-psychopharmacology and Biological Psychiatry. - 0278-5846 .- 1878-4216. ; 26:2, s. 303-306
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to study short- and long-term effects of repeated ethanol administration on nociceptin/orphanin FQ (N/OFQ) tissue concentrations in rat brain with radioimmunoassay. Animals were given either ethanol (intraperitoneal) or saline for 13 consecutive days. N/OFQ levels were examined at 30 min, 5 days and 21 days after the last dose on day 13. Ethanol-treated rats had significantly decreased N/OFQ tissue concentration in the hippocampus at 30 min after the last dose. N/OFQ levels were decreased in the cingulate cortex at 5 days after cessation of ethanol administration whereas no significant changes were found at 21 days. There were no significant changes in N/OFQ tissue concentrations at any time point studied in the mesolimbic dopamine (DA) system, a brain area associated with ethanol-induced activation. However, the results indicate that repeated ethanol administration may induce short- and long-term changes in N/OFQ tissue concentrations in other brain regions innervated with dopaminergic neurons.
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| 15. |
- Lindholm, Sara, et al.
(författare)
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Repeated ethanol administration induces short- and long-term changes in enkephalin and dynorphin tissue concentrations in rat brain
- 2000
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Ingår i: Alcohol. - 0741-8329 .- 1873-6823. ; 22:3, s. 165-171
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Tidskriftsartikel (refereegranskat)abstract
- Recently, we have shown that rats repeatedly treated with ethanol and/or cocaine have decreased kappa-opioid receptor mRNA levels in the mesolimbic system. The aim of the present study was to investigate the short- and long-term effects of repeated ethanol administration on opioid peptide concentrations in brain tissue of male Sprague-Dawley rats. Dynorphin B (1-13) (Dyn B) and Met-enkephalinArg(6)Phe(7) (MEAP), endogenous ligands to kappa- and delta-opioid receptors, respectively, were measured using radioimmunoassays. The rats were given either ethanol [intraperitoneal (ip), twice daily, 2 g/kg bw/dose] or saline for 13 consecutive days. Thirty minutes after the last ethanol dose on Day 13, the Dyn B tissue concentration was significantly decreased in the cingulate cortex. The MEAP tissue concentration was decreased in the hippocampus 5 days after the last ethanol injection as compared to saline-treated controls. Furthermore, the Dyn B and the MEAP concentrations were increased in the periaqueductal grey area (PAG) at this time point. Of particular interest were the significant increases in Dyn B tissue concentrations found in the nucleus accumbens (NAcc) at 30 min and at 21 days after the last ethanol dose. The results suggest that repeated ethanol administration induces both short- and long-term changes in the tissue concentrations of opioids in certain brain regions associated with motivation and reward.
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| 16. |
- Movérare-Skrtic, Sofia, et al.
(författare)
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Osteoblast-derived WNT16 represses osteoclastogenesis and prevents cortical bone fragility fractures.
- 2014
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Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 20:11, s. 1279-88
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Tidskriftsartikel (refereegranskat)abstract
- The WNT16 locus is a major determinant of cortical bone thickness and nonvertebral fracture risk in humans. The disability, mortality and costs caused by osteoporosis-induced nonvertebral fractures are enormous. We demonstrate here that Wnt16-deficient mice develop spontaneous fractures as a result of low cortical thickness and high cortical porosity. In contrast, trabecular bone volume is not altered in these mice. Mechanistic studies revealed that WNT16 is osteoblast derived and inhibits human and mouse osteoclastogenesis both directly by acting on osteoclast progenitors and indirectly by increasing expression of osteoprotegerin (Opg) in osteoblasts. The signaling pathway activated by WNT16 in osteoclast progenitors is noncanonical, whereas the pathway activated in osteoblasts is both canonical and noncanonical. Conditional Wnt16 inactivation revealed that osteoblast-lineage cells are the principal source of WNT16, and its targeted deletion in osteoblasts increases fracture susceptibility. Thus, osteoblast-derived WNT16 is a previously unreported key regulator of osteoclastogenesis and fracture susceptibility. These findings open new avenues for the specific prevention or treatment of nonvertebral fractures, a substantial unmet medical need.
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| 17. |
- Voisin, Sarah, et al.
(författare)
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Exercise is associated with younger methylome and transcriptome profiles in human skeletal muscle
- 2024
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Ingår i: Aging Cell. - 1474-9726. ; , s. 1-15
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Tidskriftsartikel (refereegranskat)abstract
- Exercise training prevents age-related decline in muscle function. Targeting epigenetic aging is a promising actionable mechanism and late-life exercise mitigates epigenetic aging in rodent muscle. Whether exercise training can decelerate, or reverse epigenetic aging in humans is unknown. Here, we performed a powerful meta-analysis of the methylome and transcriptome of an unprecedented number of human skeletal muscle samples (n = 3176). We show that: (1) individuals with higher baseline aerobic fitness have younger epigenetic and transcriptomic profiles, (2) exercise training leads to significant shifts of epigenetic and transcriptomic patterns toward a younger profile, and (3) muscle disuse "ages" the transcriptome. Higher fitness levels were associated with attenuated differential methylation and transcription during aging. Furthermore, both epigenetic and transcriptomic profiles shifted toward a younger state after exercise training interventions, while the transcriptome shifted toward an older state after forced muscle disuse. We demonstrate that exercise training targets many of the age-related transcripts and DNA methylation loci to maintain younger methylome and transcriptome profiles, specifically in genes related to muscle structure, metabolism, and mitochondrial function. Our comprehensive analysis will inform future studies aiming to identify the best combination of therapeutics and exercise regimes to optimize longevity.
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| 18. |
- Windahl, Sara H, 1971, et al.
(författare)
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Identification of Target Cells for the Genomic Effects of Estrogens in Bone
- 2007
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Ingår i: Endocrinology. - : The Endocrine Society. - 0013-7227 .- 1945-7170. ; 148:12, s. 5688-95
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Tidskriftsartikel (refereegranskat)abstract
- Estrogen has bone protective effects, but the exact mechanism behind these effects remains unclear. The aim of the present study was to identify the primary target cells in bone for the classical genomic effects of estrogens in vivo. For this purpose we have used reporter mice with a luciferase gene under the control of three estrogen-responsive elements (EREs), enabling detection of in vivo activation of gene transcription. Three-month-old ovariectomized mice were treated with a single dose (50microg/kg) 17beta-estradiol (E2). Luciferase activity was analysed in several tissues and in different bone marrow-derived lymphocyte enriched/depleted preparations using MacsMouse CD19 (for B lymphocytes) or CD90 (for T lymphocytes) MicroBeads. Histological characterization of cells with high luciferase content was performed using immunohistochemistry. Both cortical bone and bone marrow displayed a rapid (within 1h) and pronounced E2-induced increase in luciferase activity. The luciferase activity in total bone marrow and in bone marrow depleted of lymphocytes was increased 6-8 times more than in either B lymphocyte and T lymphocyte enriched cell fractions 4h after the E2-injection, demonstrating that mature lymphocytes are not major direct targets for the genomic effect of estrogens in bone. Immunohistochemistry identified clear luciferase staining in hypertrophic growth plate chondrocytes, megakaryocytes, osteoblasts and lining cells, while no staining was seen in proliferative chondrocyte. Although most of the osteocytes did not display any detectable luciferase staining, a subpopulation of osteocytes both in cortical and trabecular bone stained positive for luciferase. In conclusion, hypertrophic growth plate chondrocytes, megakaryocytes, osteoblasts, lining cells and a subpopulation of osteocytes were identified to respond to estrogen via the classical ERE-mediated genomic pathway in bone. Furthermore, our findings indicate that possible direct estrogenic effects on the majority of osteocytes, not staining positive for luciferase, on proliferative chondrocytes and on mature lymphocytes are mediated by non-ERE actions.
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| 19. |
- Windahl, Sara H, 1971, et al.
(författare)
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The role of the G protein-coupled receptor GPR30 in the effects of estrogen in ovariectomized mice.
- 2009
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Ingår i: American journal of physiology. Endocrinology and metabolism. - : American Physiological Society. - 0193-1849 .- 1522-1555. ; 296:3
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Tidskriftsartikel (refereegranskat)abstract
- In vitro studies suggest that the membrane G protein-coupled receptor GPR30 is a functional estrogen receptor (ER). The aim of the present study was to determine the possible in vivo role of GPR30 as a functional ER primarily for the regulation of skeletal parameters, including bone mass and longitudinal bone growth, but also for some other well-known estrogen-regulated parameters, including uterine weight, thymus weight, and fat mass. Three-month-old ovariectomized (OVX) GPR30-deficient mice (GPR30(-/-)) and wild-type (WT) mice were treated with either vehicle or increasing doses of estradiol (E(2); 0, 30, 70, 160, or 830 ng.mouse(-1).day(-1)). Body composition [bone mineral density (BMD), fat mass, and lean mass] was analyzed by dual-energy-X ray absorptiometry, while the cortical and trabecular bone compartments were analyzed by peripheral quantitative computerized tomography. Quantitative histological analyses were performed in the distal femur growth plate. Bone marrow cellularity and distribution were analyzed using a fluorescence-activated cell sorter. The estrogenic responses on most of the investigated parameters, including increase in bone mass (total body BMD, spine BMD, trabecular BMD, and cortical bone thickness), increase in uterine weight, thymic atrophy, fat mass reduction, and increase in bone marrow cellularity, were similar for all of the investigated E(2) doses in WT and GPR30(-/-) mice. On the other hand, E(2) treatment reduced longitudinal bone growth, reflected by decreased femur length and distal femur growth plate height, in the WT mice but not in the GPR30(-/-) mice compared with vehicle-treated mice. These in vivo findings demonstrate that GPR30 is not required for normal estrogenic responses on several major well-known estrogen-regulated parameters. In contrast, GPR30 is required for a normal estrogenic response in the growth plate.
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| 20. |
- Xu, Hong, et al.
(författare)
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Association between cholinesterase inhibitors and kidney function decline in patients with Alzheimers dementia
- 2023
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Ingår i: Kidney International. - : ELSEVIER SCIENCE INC. - 0085-2538 .- 1523-1755. ; 103:1, s. 166-176
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Tidskriftsartikel (refereegranskat)abstract
- Preclinical evidence shows that activation of the cholinergic anti-inflammatory pathway (CAP) may have direct and indirect beneficial effects on the kidney. Cholinesterase inhibitors (ChEIs) are specific Alzheimers dementia (AD) therapies that block the action of cholinesterases and activate CAP. Here, we explored a plausible effect of ChEIs on slowing kidney function decline by comparing the risk of CKD progression among patients with newly diagnosed AD that initiated ChEI or not within 90 days. Using complete information of routine serum creatinine tests, we evaluated changes in estimated glomerular filtration rate (eGFR) and defined the outcome of chronic kidney disease (CKD) progression as the composite of an eGFR decline of over 30%, initiation of dialysis/transplant or death attributed to CKD. A secondary outcome was death. Inverse probability of treatment-weighted Cox regression was used to estimate hazard ratios. Among 11, 898 patients, 6,803 started on ChEIs and 5,095 did not. Mean age was 80 years During a median 3.0 years of follow-up, and compared to non-use, ChEI use was associated with 18% lower risk of 95% confidence interval 0.71-0.96) and a 21% lower risk of death (0.79; 0.72-0.86). Results were consistent across subgroups, ChEI subclasses and after accounting for competing risks. Thus, in patients with AD undergoing routine care, use of ChEI (vs no-use) was associated with lower risk of CKD progression.
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