| 41. |
- Kaltsouni, Elisavet, et al.
(författare)
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Selective progesterone receptor modulation and brain activity at rest in patients with premenstrual dysphoric disorder
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Ovarian hormones have been indicated to impact brain connectivity and mood. However, there is no consistent evidence on hormone-dependent functional connectivity and mental health. Alterations in resting state networks have been suggested as markers of affective disorders, but only preliminary evidence is provided on premenstrual dysphoric disorder, in which symptoms occur upon fluctuations of ovarian hormones. Recently, three-month low-dose selective progesterone receptor modulator (SPRM) administration has been associated with symptom relief and altered task-based brain reactivity during a reactive aggression condition. The present study sought to investigate the effect of this treatment on resting state functional connectivity (rs-FC) in patients with PMDD. Seed-based analyses were conducted, including including seeds from the classic resting state networks along with the functional cluster affected by SPRM treatment. Within previously identified networks related with emotional processing, rs-FC was compared between individuals with PMDD during the symptomatic luteal phase before randomization to treatment or placebo and during the end of the last treatment cycle. Seed-based rs-FC analyses yielded significant treatment by time effects on rs-FC between the left posterior superior temporal gyrus and the right insula cortex, between the posterior cerebellum and the left temporal pole, and between the right lateral visual network and left superior frontal gyrus. Visuo-frontal luteal phase connectivity decreased for the SPRM group and was positively correlated with changes in mood symptom severity in the placebo group. Cerebellar and temporal connectivity increased for the SPRM treatment group, while temporo-insular connectivity decreased and was positively correlated with cortisol levels. These findings indicate that SPRM treatment influenced rs-FC, which could be a relevant mechanism behind symptom alleviation.
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| 42. |
- Willighagen, Egon, 1974-, et al.
(författare)
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Linking the Resource Description Framework to cheminformatics and proteochemometrics
- 2011
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Ingår i: Journal of Biomedical Semantics. - 2041-1480. ; 2:Suppl 1, s. 6-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND :Semantic web technologies are finding their way into the life sciences. Ontologies and semantic markup have already been used for more than a decade in molecular sciences, but have not found widespread use yet. The semantic web technology Resource Description Framework (RDF) and related methods show to be sufficiently versatile to change that situation.RESULTS :The work presented here focuses on linking RDF approaches to existing molecular chemometrics fields, including cheminformatics, QSAR modeling and proteochemometrics. Applications are presented that link RDF technologies to methods from statistics and cheminformatics, including data aggregation, visualization, chemical identification, and property prediction. They demonstrate how this can be done using various existing RDF standards and cheminformatics libraries. For example, we show how IC50 and Ki values are modeled for a number of biological targets using data from the ChEMBL database.CONCLUSIONS :We have shown that existing RDF standards can suitably be integrated into existing molecular chemometrics methods. Platforms that unite these technologies, like Bioclipse, makes this even simpler and more transparent. Being able to create and share workflows that integrate data aggregation and analysis (visual and statistical) is beneficial to interoperability and reproducibility. The current work shows that RDF approaches are sufficiently powerful to support molecular chemometrics workflows.
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| 43. |
- Lundgren, Magnus, 1981-
(författare)
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Coxsackievirus B3 Infection and Host Defence Responses Change the Metabolism of PBDE
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- It has been suggested that the rising amounts of chemicals in the environment may affect host resistance and increase susceptibility to infections. Studies have also shown that infections can change the toxicity of pollutants. The aim of this thesis was to study interactions between environmental pollutant exposure in terms of polybrominated diphenyl ethers (PBDE) and a common human coxsackievirus B3 (CVB3) infection adapted to Balb/c mice. The studies focused on virus levels, cytokines, metabolising cytochrome P450 (CYP) enzymes and tissue distribution of PBDE. A novel finding was an organ-specific effect of CVB3 infection on the metabolising capacity of PBDE. The PBDE metabolising enzyme CYP2B10 was down-regulated by the CVB3 infection in the liver, up-regulated in the lungs, but not affected in the pancreas. Accordingly, CVB3 infection increased the concentration of PBDE in the livers of infected mice. However, serum levels of PBDE were not affected by the infection, indicating that serum does not reflect the actual organ exposure of PBDE in infected individuals. The change in metabolising capacity was likely mediated by infection-induced cytokines and associated effects on the nuclear factor-κB (NF-κB) pathway. PBDE drastically decreased serum levels of several cytokines and chemokines, an event that may create a slot for viruses to replicate. Accordingly, some results show that infected mice exposed to a high dose of PBDE had higher virus levels than mice exposed to a low dose. In conclusion, infected individuals showed organ-specific changes in metabolism and tissue levels of PBDE, which potentially could change the toxicity of PBDE. PBDE also seems to affect the fate of the infection. NF-κB activated pathways may mediate one possible mechanism underlying these effects. Thus, further investigations of this pathway are warranted. In addition, future studies should address how PBDE exposure affects viral replication.
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| 44. |
- Belfrage, Per, et al.
(författare)
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Alterations of lipid metabolism in healthy volunteers during long-term ethanol intake
- 1977
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Ingår i: European Journal of Clinical Investigation. - : Wiley. - 0014-2972 .- 1365-2362. ; 7:2, s. 127-131
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Tidskriftsartikel (refereegranskat)abstract
- Nine young, healthy male volunteers were given ethanol (75 g/day) for 5 weeks. The ethanol was divided into five daily doses and taken so that blood ethanol levels never exceeded 0.04% (w/v). During the latter part of the ethanol intake period, there was a significant, transient increase of plasma triglyceride (TG) concentrations followed by reduction to normal levels. A three-fold increase of lipoprotein lipase activity (LLA) occurred in biopsy specimens of adipose tissue. An increase of alpha-lipoprotein concentrations, which correlated significantly with the decrease in plasma TG levels and the increase in adipose LLA, was also observed during the ethanol intake period. No changes were observed in plasma cholesterol and beta-lipoprotein levels. A transient, three-fold increase of TG concentrations occurred in liver biopsy specimens. Ultrastructural and cytochemical examinations of the biopsy specimens showed hyperplasia of the smooth endoplasmic reticulum, and increased canallicular activity of gamma-glutamyl transferase (gamma-GT) activity in most subjects towards the end of and after the ethanol intake period. Serum gamma-GT levels also increased significantly.
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| 45. |
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| 46. |
- Brage, M, et al.
(författare)
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Different cysteine proteinases involved in bone resorption and osteoclast formation.
- 2005
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Ingår i: Calcified tissue international. - : Springer Science and Business Media LLC. - 0171-967X .- 1432-0827. ; 76:6, s. 439-47
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Tidskriftsartikel (refereegranskat)abstract
- Cysteine proteinases, especially cathepsin K, play an important role in osteoclastic degradation of bone matrix proteins and the process can, consequently, be significantly inhibited by cysteine proteinase inhibitors. We have recently reported that cystatin C and other cysteine proteinase inhibitors also reduce osteoclast formation. However, it is not known which cysteine proteinase(s) are involved in osteoclast differentiation. In the present study, we compared the relative potencies of cystatins C and D as inhibitors of bone resorption in cultured mouse calvariae, osteoclastogenesis in mouse bone marrow cultures, and cathepsin K activity. Inhibition of cathepsin K activity was assessed by determining equilibrium constants for inhibitor complexes in fluorogenic substrate assays. The data demonstrate that whereas human cystatins C and D are equipotent as inhibitors of bone resorption, cystatin D is 10-fold less potent as an inhibitor of osteoclastogenesis and 200-fold less potent as an inhibitor of cathepsin K activity. A recombinant human cystatin C variant with Gly substitutions for residues Arg8, Leu9, Val10, and Trp106 did not inhibit bone resorption, had 1,000-fold decreased inhibitory effect on cathepsin K activity compared to wildtype cystatin C, but was equipotent with wildtype cystatin C as an inhibitor of osteoclastogenesis. It is concluded that (i) different cysteine proteinases are likely to be involved in bone resorption and osteoclast formation, (ii) cathepsin K may not be an exclusive target enzyme in any of the two systems, and (iii) the enzyme(s) involved in osteoclastogenesis might not be a typical papain-like cysteine proteinase.
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| 47. |
- Tour, Jeanette, et al.
(författare)
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Gene-to-gene interactions regulate endogenous pain modulation in fibromyalgia patients and healthy controls-antagonistic effects between opioid and serotonin-related genes.
- 2017
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Ingår i: Pain. - : Ovid Technologies (Wolters Kluwer Health). - 0304-3959 .- 1872-6623. ; 158:7, s. 1194-1203
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Tidskriftsartikel (refereegranskat)abstract
- Chronic pain is associated with dysfunctional endogenous pain modulation, involving both central opioid and serotonergic (5-HT) signaling. Fibromyalgia (FM) is a chronic pain syndrome, characterized by widespread musculoskeletal pain and reduced exercise-induced hypoalgesia (EIH). In this study, we assessed the effects of 3 functional genetic polymorphisms on EIH in 130 patients with FM and 132 healthy controls. Subjects were genotyped regarding the mu-opioid receptor (OPRM1) gene (rs1799971), the serotonin transporter (5-HTT) gene (5-HTTLPR/rs25531), and the serotonin-1a receptor (5-HT1a) gene (rs6296). The patients with FM had increased pain sensitivity and reduced EIH compared with healthy controls. None of the polymorphisms had an effect on EIH on their own. We found significant gene-to-gene interactions between OPRM1 x 5-HTT and OPRM1 x 5-HT1a regarding activation of EIH, with no statistically significant difference between groups. Better EIH was found in individuals with genetically inferred strong endogenous opioid signaling (OPRM1 G) in combination with weak 5-HT tone (5-HTT low/5-HT1a G), compared with strong 5-HT tone (5-HTT high/5-HT1a CC). Based on the proposed mechanisms of these genetic variants, the findings indicate antagonistic interactions between opioid and serotonergic mechanisms during EIH. Moreover, despite different baseline pain level, similar results were detected in FM and controls, not supporting an altered interaction between opioid and 5-HT mechanisms as the basis for dysfunction of EIH in patients with FM. In summary, our results suggest that, by genetic association, the mu-opioid receptor interacts with 2 major serotonergic structures involved in 5-HT reuptake and release, to modulate EIH.
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| 48. |
- Altay, Özlem, et al.
(författare)
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Current Status of COVID-19 Therapies and Drug Repositioning Applications
- 2020
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Ingår i: Iscience. - : Elsevier BV. - 2589-0042. ; 23:7
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Tidskriftsartikel (refereegranskat)abstract
- The rapid and global spread of a new human coronavirus (SARS-CoV-2) has produced an immediate urgency to discover promising targets for the treatment of COVID-19. Drug repositioning is an attractive approach that can facilitate the drug discovery process by repurposing existing pharmaceuticals to treat illnesses other than their primary indications. Here, we review current information concerning the global health issue of COVID-19 including promising approved drugs and ongoing clinical trials for prospective treatment options. In addition, we describe computational approaches to be used in drug repurposing and highlight examples of in silico studies of drug development efforts against SARS-CoV-2.
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| 49. |
- Midlöv, Patrik, et al.
(författare)
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Medication report reduces number of medication errors when elderly patients are discharged from hospital
- 2008
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Ingår i: PHARMACY WORLD & SCIENCE. - : Springer Science and Business Media LLC. - 0928-1231 .- 1573-739X. ; 30:1, s. 92-98
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Tidskriftsartikel (refereegranskat)abstract
- Objective To investigate whether a Medication Report can reduce the number of medication errors when elderly patients are discharged from hospital. Method We conducted a prospective intervention with retrospective controls on patients at three departments at Lund University Hospital, Sweden that where transferred to primary care. The intervention group, where patients received a Medication Report at discharge, was compared with a control group with patients of the same age, who were not given a Medication Report when discharged from the same ward one year earlier. Main outcome measures The main outcome measure was the number of medication errors when elderly patients were discharged from hospital. Results Among 248 patients in the intervention group 79 (32%) had at least one medication error as compared with 118 (66%) among the 179 patients in the control group. In the intervention group 15% of the patients had errors that were considered to have moderate or high risk of clinical consequences compared with 32% in the control group. The differences were statistically significant (P < 0.001). Conclusion Medication errors are common when elderly patients are discharged from hospital. The Medication Report is a simple tool that reduces the number of medication errors.
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| 50. |
- Björk, Jonas, et al.
(författare)
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A new tool for predicting the probability of chronic kidney disease from a specific value of estimated GFR.
- 2010
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Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation. - : Informa UK Limited. - 1502-7686 .- 0036-5513. ; Jul 1, s. 327-333
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Objective. To demonstrate how patients' probability of having chronic kidney disease (CKD) stage 3-5 (measured GFR <60 mL/min/1.73 m(2)) can be predicted from a specific value of estimated glomerular filtration rate (eGFR). Material and methods. The probability of CKD stage 3-5 was predicted from a logistic regression model (n = 850) using three different eGFR prediction equations: Lund-Malmö, MDRD and CKD-EPI. Population weighting was used to illustrate how this probability varies in three different populations: original sample (55% true prevalence of CKD stage 3-5), a screening (6.7% prevalence) and a CKD population (84% prevalence). Results. All three eGFR-equations had high classification ability (area under the receiver-operating-characteristic curve = 97%). The probability of CKD stage 3-5 increased with decreasing eGFR, varied substantially among the populations studied and to some extent between the eGFR-equations. Using the Lund-Malmö equation as illustration, the probability of CKD stage 3-5 is > 90% only when eGFR is <38 mL/min/1.73 m(2) in a screening population, whereas it is > 90% already when eGFR is <51 mL/min/1.73 m(2) in a CKD population. Conversely, the probability of CKD stage 3-5 is <10% if eGFR > 59 mL/min/1.73 m(2) in a screening population, whereas it is <10% only when eGFR is > 88 mL/min/1.73 m(2) in a CKD population. Conclusion. Instead of reporting diagnostic accuracy as sensitivity, specificity, and predictive values, actual eGFR supplemented with the probability that it represents a true GFR <60 mL/min/1.73 m(2) may be more valuable for physicians. Clinical (pre-test) probability in the population must be considered when predicting this probability.
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