| 1. |
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
- Ajello, M., et al.
(författare)
-
Gamma Rays from Fast Black-hole Winds
- 2021
-
Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 921:2
-
Tidskriftsartikel (refereegranskat)abstract
- Massive black holes at the centers of galaxies can launch powerful wide-angle winds that, if sustained over time, can unbind the gas from the stellar bulges of galaxies. These winds may be responsible for the observed scaling relation between the masses of the central black holes and the velocity dispersion of stars in galactic bulges. Propagating through the galaxy, the wind should interact with the interstellar medium creating a strong shock, similar to those observed in supernovae explosions, which is able to accelerate charged particles to high energies. In this work we use data from the Fermi Large Area Telescope to search for the gamma-ray emission from galaxies with an ultrafast outflow (UFO): a fast (v similar to 0.1 c), highly ionized outflow, detected in absorption at hard X-rays in several nearby active galactic nuclei (AGN). Adopting a sensitive stacking analysis we are able to detect the average gamma-ray emission from these galaxies and exclude that it is due to processes other than UFOs. Moreover, our analysis shows that the gamma-ray luminosity scales with the AGN bolometric luminosity and that these outflows transfer similar to 0.04% of their mechanical power to gamma-rays. Interpreting the observed gamma-ray emission as produced by cosmic rays (CRs) accelerated at the shock front, we find that the gamma-ray emission may attest to the onset of the wind-host interaction and that these outflows can energize charged particles up to the transition region between galactic and extragalactic CRs.
|
|
| 8. |
|
|
| 9. |
- Busca, A, et al.
(författare)
-
Outcome of COVID-19 in allogeneic stem cell transplant recipients: Results from the EPICOVIDEHA registry
- 2023
-
Ingår i: Frontiers in immunology. - : Frontiers Media SA. - 1664-3224. ; 14, s. 1125030-
-
Tidskriftsartikel (refereegranskat)abstract
- The outcome of COVID-19 in allogeneic hematopoietic stem cell transplantation (HSCT) recipients is almost uniformely considered poor. The aim of present study was to retrospectively analyse the outcome and risk factors for mortality in a large series of patients who developed COVID-19 infection after an allogeneic HSCT.MethodsThis multicenter retrospective study promoted by the European Hematology Association – Infections in Hematology Study Working Group, included 326 adult HSCT patients who had COVID-19 between January 2020 and March 2022.ResultsThe median time from HSCT to the diagnosis of COVID-19 was 268 days (IQR 86-713; range 0-185 days). COVID-19 severity was mild in 21% of the patients, severe in 39% and critical in 16% of the patients. In multivariable analysis factors associated with a higher risk of mortality were, age above 50 years, presence of 3 or more comorbidities, active hematologic disease at time of COVID-19 infection, development of COVID-19 within 12 months of HSCT, and severe/critical infections. Overall mortality rate was 21% (n=68): COVID-19 was the main or secondary cause of death in 16% of the patients (n=53).ConclusionsMortality in HSCT recipients who develop COVID-19 is high and largely dependent on age, comorbidities, active hematologic disease, timing from transplant and severity of the infection.
|
|
| 10. |
|
|
| 11. |
|
|
| 12. |
- Marchesi, F, et al.
(författare)
-
COVID-19 in adult acute myeloid leukemia patients: a long-term follow-up study from the European Hematology Association survey (EPICOVIDEHA)
- 2023
-
Ingår i: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 1592-8721 .- 0390-6078. ; 108:1, s. 22-33
-
Tidskriftsartikel (refereegranskat)abstract
- Patients with acute myeloid leukemia (AML) are at high risk of dying from coronavirus disease 2019 (COVID-19). The optimal management of AML patients with COVID-19 has not been established. Our multicenter study included 388 adult AML patients diagnosed with COVID-19 between February 2020 and October 2021. The vast majority were receiving or had received AML treatment in the preceding 3 months. COVID-19 was severe in 41.2% and critical in 21.1% of cases. The chemotherapeutic schedule was modified in 174 patients (44.8%), delayed in 68 and permanently discontinued in 106. After a median follow-up of 325 days, 180 patients (46.4%) had died; death was attributed to COVID-19 (43.3%), AML (26.1%) or to a combination of both (26.7%), whereas in 3.9% of cases the reason was unknown. Active disease, older age, and treatment discontinuation were associated with death, whereas AML treatment delay was protective. Seventy-nine patients had a simultaneous AML and COVID-19 diagnosis, with better survival when AML treatment could be delayed (80%; P<0.001). Overall survival in patients with a diagnosis of COVID-19 between January 2020 and August 2020 was significantly lower than that in patients diagnosed between September 2020 and February 2021 and between March 2021 and September 2021 (39.8% vs. 60% vs. 61.9%, respectively; P=0.006). COVID-19 in AML patients was associated with a high mortality rate and modifications of therapeutic algorithms. The best approach to improve survival was to delay AML treatment, whenever possible.
|
|
| 13. |
|
|
| 14. |
|
|
| 15. |
- Cattaneo, C, et al.
(författare)
-
Simultaneous Onset of Haematological Malignancy and COVID: An Epicovideha Survey
- 2022
-
Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 14:22
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The outcome of patients with simultaneous diagnosis of haematological malignancies (HM) and COVID-19 is unknown and there are no specific treatment guidelines. Methods: We describe the clinical features and outcome of a cohort of 450 patients with simultaneous diagnosis of HM and COVID-19 registered in the EPICOVIDEHA registry between March 2020 to February 2022. Results: Acute leukaemia and lymphoma were the most frequent HM (35.8% and 35.1%, respectively). Overall, 343 (76.2%) patients received treatment for HM, which was delayed for longer than one month since diagnosis in 57 (16.6%). An overall response rate was observed in 140 (40.8%) patients after the first line of treatment. After a median follow-up of 35 days, overall mortality was 177/450 (39.3%); 30-day mortality was significantly higher in patients not receiving HM treatment (42.1%) than in those receiving treatment (27.4%, p = 0.004), either before and/or after COVID-19, or compared to patients receiving HM treatment at least after COVID-19 (15.2%, p < 0.001). Age, severe/critical COVID-19, ≥2 comorbidities, and lack of HM treatment were independent risk factors for mortality, whereas a lymphocyte count >500/mcl at COVID-19 onset was protective. Conclusions: HM treatment should be delivered as soon as possible for patients with simultaneous diagnosis of COVID-19 and HM requiring immediate therapy.
|
|
| 16. |
|
|
| 17. |
|
|
| 18. |
- Ovadia, C., et al.
(författare)
-
Ursodeoxycholic acid enriches intestinal bile salt hydrolase-expressing Bacteroidetes in cholestatic pregnancy
- 2020
-
Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
-
Tidskriftsartikel (refereegranskat)abstract
- Ursodeoxycholic acid (UDCA) treatment can reduce itch and lower endogenous serum bile acids in intrahepatic cholestasis of pregnancy (ICP). We sought to determine how it could influence the gut environment in ICP to alter enterohepatic signalling. The gut microbiota and bile acid content were determined in faeces from 35 pregnant women (14 with uncomplicated pregnancies and 21 with ICP, 17 receiving UDCA). Faecal bile salt hydrolase activity was measured using a precipitation assay. Serum fibroblast growth factor 19 (FGF19) and 7α-hydroxy-4-cholesten-3-one (C4) concentrations were measured following a standardised diet for 21 hours. Women with a high ratio of Bacteroidetes to Firmicutes were more likely to be treated with UDCA (Fisher’s exact test p = 0.0178) than those with a lower ratio. Bile salt hydrolase activity was reduced in women with low Bacteroidetes:Firmicutes. Women taking UDCA had higher faecal lithocholic acid (p < 0.0001), with more unconjugated bile acids than women with untreated ICP or uncomplicated pregnancy. UDCA-treatment increased serum FGF19, and reduced C4 (reflecting lower bile acid synthesis). During ICP, UDCA treatment can be associated with enrichment of the gut microbiota with Bacteroidetes. These demonstrate high bile salt hydrolase activity, which deconjugates bile acids enabling secondary modification to FXR agonists, enhancing enterohepatic feedback via FGF19. © 2020, The Author(s).
|
|
| 19. |
|
|
| 20. |
- Marchetti, M, et al.
(författare)
-
Outcomes of SARS-CoV-2 infection in Ph-neg chronic myeloproliferative neoplasms: results from the EPICOVIDEHA registry
- 2023
-
Ingår i: Therapeutic advances in hematology. - : SAGE Publications. - 2040-6207 .- 2040-6215. ; 14, s. 20406207231154706-
-
Tidskriftsartikel (refereegranskat)abstract
- Patients with Philadelphia-negative chronic myeloproliferative neoplasms (MPN) typically incur high rates of infections and both drugs and comorbidities may modulate infection risk. Objectives: The present study aims to assess the effect of immunosuppressive agents on clinical outcomes of MPN patients affected by the coronavirus disease 2019 (COVID-19). Design: This is an observational study. Methods: We specifically searched and analyzed MPN patients collected by EPICOVIDEHA online registry, which includes individuals with hematological malignancies diagnosed with COVID-19 since February 2020. Results: Overall, 398 patients with MPN were observed for a median of 76 days [interquartile range (IQR): 19–197] after detection of SARS-CoV2 infection. Median age was 69 years (IQR: 58–77) and 183 individuals (46%) had myelofibrosis (MF). Overall, 121 patients (30%) of the whole cohort received immunosuppressive therapies including steroids, immunomodulatory drugs, or JAK inhibitors. Hospitalization and consecutive admission to intensive care unit was required in 216 (54%) and 53 patients (13%), respectively. Risk factors for hospital admission were identified by multivariable logistic regression and include exposure to immunosuppressive therapies [odds ratio (OR): 2.186; 95% confidence interval (CI): 1.357–3.519], age ⩾70 years, and comorbidities. The fatality rate was 22% overall and the risk of death was independently increased by age ⩾70 years [hazard ratio (HR): 2.191; 95% CI: 1.363–3.521], previous comorbidities, and exposure to immunosuppressive therapies before the infection (HR: 2.143; 95% CI: 1.363–3.521). Conclusion: COVID-19 infection led to a particularly dismal outcome in MPN patients receiving immunosuppressive agents or reporting multiple comorbidities. Therefore, specific preventive strategies need to be tailored for such individuals. Plain language summary EPICOVIDEHA registry reports inferior outcomes of COVID-19 in patients with Philadelphia-negative chronic myeloproliferative neoplasms receiving immunosuppressive therapies. Patients with Philadelphia-negative chronic myeloproliferative neoplasms (MPN) incur high rates of infections during the course of their disease. The present study was aimed at assessing which patient characteristics predicted a worse outcome of SARS-COV-2 infection in individuals with MPN. To pursue this objective, the researchers analyzed the data collected by EPICOVIDEHA, an international online registry, which includes individuals with hematological malignancies diagnosed with COVID-19 since February 2020. The database provided clinical data of 398 patients with MPN incurring COVID-19: Patients were mostly elderly (median age was 69 years); Forty-six percent of them were affected by myelofibrosis, which is the most severe MPN; Moreover, 32% were receiving immunosuppressive therapies (JAK inhibitors, such as ruxolitinib, steroids, or immunomodulatory IMID drugs, such as thalidomide) before COVID-19. Hospitalization was required in 54% of the patients, and the risk of being hospitalized for severe COVID-19 was independently predicted by Older age; Comorbidities; Exposure to immunosuppressive therapies. Overall, 22% of MPN patients deceased soon after COVID-19 and the risk of death was independently increased over twofold by Older age; Comorbidities; Exposure to immunosuppressive therapies before the infection. In conclusion, COVID-19 infection led to a particularly dismal outcome in MPN patients receiving immunosuppressive agents, including JAK inhibitors, or reporting multiple comorbidities. Therefore, specific preventive strategies need to be tailored for such individuals.
|
|
| 21. |
- Marchesi, S., et al.
(författare)
-
THE CHANDRA COSMOS LEGACY SURVEY : OPTICAL/IR IDENTIFICATIONS
- 2016
-
Ingår i: Astrophysical Journal. - 0004-637X. ; 817:1
-
Forskningsöversikt (refereegranskat)abstract
- We present the catalog of optical and infrared counterparts of the Chandra COSMOS-Legacy Survey, a 4.6 Ms Chandra program on the 2.2 deg2 of the COSMOS field, combination of 56 new overlapping observations obtained in Cycle 14 with the previous C-COSMOS survey. In this Paper we report the i, K, and 3.6 μm identifications of the 2273 X-ray point sources detected in the new Cycle 14 observations. We use the likelihood ratio technique to derive the association of optical/infrared (IR) counterparts for 97% of the X-ray sources. We also update the information for the 1743 sources detected in C-COSMOS, using new K and 3.6 μm information not available when the C-COSMOS analysis was performed. The final catalog contains 4016 X-ray sources, 97% of which have an optical/IR counterpart and a photometric redshift, while ≃54% of the sources have a spectroscopic redshift. The full catalog, including spectroscopic and photometric redshifts and optical and X-ray properties described here in detail, is available online. We study several X-ray to optical (X/O) properties: with our large statistics we put better constraints on the X/O flux ratio locus, finding a shift toward faint optical magnitudes in both soft and hard X-ray band. We confirm the existence of a correlation between X/O and the the 2-10 keV luminosity for Type 2 sources. We extend to low luminosities the analysis of the correlation between the fraction of obscured AGNs and the hard band luminosity, finding a different behavior between the optically and X-ray classified obscured fraction.
|
|
| 22. |
- van Huizen, Astrid M., et al.
(författare)
-
International eDelphi Study to Reach Consensus on the Methotrexate Dosing Regimen in Patients With Psoriasis
- 2022
-
Ingår i: JAMA dermatology. - : American Medical Association (AMA). - 2168-6068 .- 2168-6084. ; 158:5, s. 561-561
-
Tidskriftsartikel (refereegranskat)abstract
- Importance A clear dosing regimen for methotrexate in psoriasis is lacking, and this might lead to a suboptimal treatment. Because methotrexate is affordable and globally available, a uniform dosing regimen could potentially optimize the treatment of patients with psoriasis worldwide.Objective To reach international consensus among psoriasis experts on a uniform dosing regimen for treatment with methotrexate in adult and pediatric patients with psoriasis and identify potential future research topics.Design, Setting, and Participants Between September 2020 and March 2021, a survey study with a modified eDelphi procedure that was developed and distributed by the Amsterdam University Medical Center and completed by 180 participants worldwide (55 [30.6%] resided in non-Western countries) was conducted in 3 rounds. The proposals on which no consensus was reached were discussed in a conference meeting (June 2021). Participants voted on 21 proposals with a 9-point scale (1-3 disagree, 4-6 neither agree nor disagree, 7-9 agree) and were recruited through the Skin Inflammation and Psoriasis International Network and European Academy of Dermatology and Venereology in June 2020. Apart from being a dermatologist/dermatology resident, there were no specific criteria for participation in the survey. The participants worked mainly at a university hospital (97 [53.9%]) and were experienced in treating patients with psoriasis with methotrexate (163 [91.6%] had more than 10 years of experience).Main Outcomes and Measures In a survey with eDelphi procedure, we tried to reach consensus on 21 proposals. Consensus was defined as less than 15% voting disagree (1-3). For the consensus meeting, consensus was defined as less than 30% voting disagree.Results Of 251 participants, 180 (71.7%) completed all 3 survey rounds, and 58 participants (23.1%) joined the conference meeting. Consensus was achieved on 11 proposals in round 1, 3 proposals in round 2, and 2 proposals in round 3. In the consensus meeting, consensus was achieved on 4 proposals. More research is needed, especially for the proposals on folic acid and the dosing of methotrexate for treating subpopulations such as children and vulnerable patients.Conclusions and Relevance In this eDelphi consensus study, consensus was reached on 20 of 21 proposals involving methotrexate dosing in patients with psoriasis. This consensus may potentially be used to harmonize the treatment with methotrexate in patients with psoriasis.
|
|
| 23. |
- Ceraj, L., et al.
(författare)
-
The XXL Survey: XLIII. The quasar radio loudness dichotomy exposed via radio luminosity functions obtained by combining results from COSMOS and XXL-S X-ray selected quasars
- 2020
-
Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 642
-
Tidskriftsartikel (refereegranskat)abstract
- We studied a sample of 274 radio and X-ray selected quasars (XQSOs) detected in the COSMOS and XXL-S radio surveys at 3 GHz and 2.1 GHz, respectively. This sample was identified by adopting a conservative threshold in X-ray luminosity, LX [2-10 keV] ≥ 1044 erg s-1, selecting only the most powerful quasars. A number of previous studies on the origin of radio emission in type-1 quasars have focused on the radio loudness distributions, some claiming to have found evidence for bimodality, pointing toward the existence of two physically different mechanisms for the radio emission. Using available multiwavelength data, we examined various criteria for the selection of radio-loud (RL) and radio-quiet (RQ) XQSOs and found that the number of RL/RQ XQSOs changes significantly depending on the chosen criterion. This discrepancy arises due to the different criteria tracing different physical processes and due to the fact that our sample was selected from flux-limited radio and X-ray surveys. Another approach to study the origin of radio emission in XQSOs is via their radio luminosity functions (RLF). We constructed the XQSO 1.4 GHz RLFs in six redshift bins at 0:5 ≤ z ≤ 3:75. The lower-1.4 GHz luminosity end shows a higher normalization than expected only from AGN contribution in all studied redshift bins. We found that the so-called "bump"is mostly dominated by emission due to star-forming processes within the host galaxies of XQSOs. As expected, AGN-related radio emission is the dominant contribution at the higher-luminosity end of RLF. To study the evolution of the XQSO RLF, we used a combination of analytic forms from the literature to constrain the "bump"due to star formation and the higher-luminosity AGN part of the RLF. We defined two 1.4 GHz luminosity thresholds, Lth;SF and Lth;AGN, below and above which more than 80% of sources contributing to the RLF are dominated by star formation and AGN-related activity, respectively. The two thresholds evolve with redshift, which is most likely driven by the strong evolution of star formation rates of the XQSO host galaxies. We found that both the lower and higher luminosity ends evolve significantly in density, while their luminosity evolution parameters are consistent with being constant. We found that the lower-luminosity end evolves both in density and luminosity, while the higher-luminosity end evolves significantly only in density. Our results expose the dichotomy of the origin of radio emission: while the higher-luminosity end of the XQSO RLF is dominated by AGN activity, the lower-luminosity end is dominated by the star formation-related processes.
|
|
| 24. |
|
|
| 25. |
- Marchesi, S., et al.
(författare)
-
THE CHANDRA COSMOS-LEGACY SURVEY : SOURCE X-RAY SPECTRAL PROPERTIES
- 2016
-
Ingår i: Astrophysical Journal. - 0004-637X. ; 830:2
-
Tidskriftsartikel (refereegranskat)abstract
- We present the X-ray spectral analysis of the 1855 extragalactic sources in the Chandra COSMOS-Legacy survey catalog having more than 30 net counts in the 0.5-7 keV band. A total of 38% of the sources are optically classified type 1 active galactic nuclei (AGNs), 60% are type 2 AGNs, and 2% are passive, low-redshift galaxies. We study the distribution of AGN photon index Γ and of the intrinsic absorption based on the sources' optical classification: type 1 AGNs have a slightly steeper mean photon index Γ than type 2 AGNs, which, on the other hand, have average times higher than type 1 AGNs. We find that ∼15% of type 1 AGNs have cm-2, i.e., are obscured according to the X-ray spectral fitting; the vast majority of these sources have 1044 erg s-1. The existence of these objects suggests that optical and X-ray obscuration can be caused by different phenomena, the X-ray obscuration being, for example, caused by dust-free material surrounding the inner part of the nuclei. Approximately 18% of type 2 AGNs have cm-2, and most of these sources have low X-ray luminosities (L2-10keV < 1043 erg s-1). We expect a part of these sources to be low-accretion, unobscured AGNs lacking broad emission lines. Finally, we also find a direct proportional trend between and host-galaxy mass and star formation rate, although part of this trend is due to a redshift selection effect.
|
|
| 26. |
- McIlvride, Saraid, et al.
(författare)
-
Obeticholic acid ameliorates dyslipidemia but not glucose tolerance in mouse model of gestational diabetes.
- 2019
-
Ingår i: American journal of physiology. Endocrinology and metabolism. - : American Physiological Society. - 1522-1555 .- 0193-1849. ; 317:2
-
Tidskriftsartikel (refereegranskat)abstract
- Metabolism alters markedly with advancing gestation, characterized by progressive insulin resistance, dyslipidemia, and raised serum bile acids. The nuclear receptor farnesoid X receptor (FXR) has an integral role in bile acid homeostasis and modulates glucose and lipid metabolism. FXR is known to be functionally suppressed in pregnancy. The FXR agonist, obeticholic acid (OCA), improves insulin sensitivity in patients with type 2 diabetes with nonalcoholic fatty liver disease. We therefore hypothesized that OCA treatment during pregnancy could improve disease severity in a mouse model of gestational diabetes mellitus (GDM). C57BL/6J mice were fed a high-fat diet (HFD; 60% kcal from fat) for 4 wk before and throughout pregnancy to induce GDM. The impact of the diet supplemented with 0.03% OCA throughout pregnancy was studied. Pregnant HFD-fed mice displayed insulin resistance and dyslipidemia. OCA significantly reduced plasma cholesterol concentrations in nonpregnant and pregnant HFD-fed mice (by 22.4%, P < 0.05 and 36.4%, P < 0.001, respectively) and reduced the impact of pregnancy on insulin resistance but did not change glucose tolerance. In nonpregnant HFD-fed mice, OCA ameliorated weight gain, reduced mRNA expression of inflammatory markers in white adipose tissue, and reduced plasma glucagon-like peptide 1 concentrations (by 62.7%, P < 0.01). However, these effects were not evident in pregnant mice. OCA administration can normalize plasma cholesterol levels in a mouse model of GDM. However, the absence of several of the effects of OCA in pregnant mice indicates that the agonistic action of OCA is not sufficient to overcome many metabolic consequences of the pregnancy-associated reduction in FXR activity.
|
|
| 27. |
- Ostaszewski, Marek, et al.
(författare)
-
COVID19 Disease Map, a computational knowledge repository of virus-host interaction mechanisms
- 2021
-
Ingår i: Molecular Systems Biology. - : John Wiley & Sons. - 1744-4292 .- 1744-4292. ; 17:10
-
Tidskriftsartikel (refereegranskat)abstract
- We need to effectively combine the knowledge from surging literature with complex datasets to propose mechanistic models of SARS-CoV-2 infection, improving data interpretation and predicting key targets of intervention. Here, we describe a large-scale community effort to build an open access, interoperable and computable repository of COVID-19 molecular mechanisms. The COVID-19 Disease Map (C19DMap) is a graphical, interactive representation of disease-relevant molecular mechanisms linking many knowledge sources. Notably, it is a computational resource for graph-based analyses and disease modelling. To this end, we established a framework of tools, platforms and guidelines necessary for a multifaceted community of biocurators, domain experts, bioinformaticians and computational biologists. The diagrams of the C19DMap, curated from the literature, are integrated with relevant interaction and text mining databases. We demonstrate the application of network analysis and modelling approaches by concrete examples to highlight new testable hypotheses. This framework helps to find signatures of SARS-CoV-2 predisposition, treatment response or prioritisation of drug candidates. Such an approach may help deal with new waves of COVID-19 or similar pandemics in the long-term perspective.
|
|
| 28. |
- Pataia, Vanessa, et al.
(författare)
-
Obeticholic acid improves fetal bile acid profile in a mouse model of gestational hypercholanemia.
- 2020
-
Ingår i: American journal of physiology. Gastrointestinal and liver physiology. - : American Physiological Society. - 1522-1547 .- 0193-1857. ; 319:2
-
Tidskriftsartikel (refereegranskat)abstract
- Intrahepatic cholestasis of pregnancy (ICP) is characterized by elevated maternal circulating bile acid levels and associated dyslipidemia. ICP leads to accumulation of bile acids in the fetal compartment and the elevated bile acid concentrations are associated with an increased risk of adverse fetal outcomes. The farnesoid X receptor agonist, obeticholic acid (OCA) is efficient in the treatment of cholestatic conditions such as primary biliary cholangitis. We hypothesized that OCA administration during hypercholanemic pregnancy will improve maternal and fetal bile acid and lipid profiles. Female C57BL/6J mice were fed either: a normal chow diet, a 0.5% cholic acid (CA)-supplemented diet, a 0.03% OCA-supplemented diet, or a 0.5% CA + 0.03% OCA-supplemented diet for 1 week prior to mating and throughout pregnancy until euthanization on day 18. The effects of CA and OCA feeding on maternal and fetal morphometry, bile acid and lipid levels, and cecal microbiota were investigated. OCA administration during gestation did not alter the maternal or fetal body weight or organ morphometry. OCA treatment during hypercholanemic pregnancy reduced bile acid levels in the fetal compartment. However, fetal dyslipidemia was not reversed, and OCA did not impact maternal bile acid levels or dyslipidemia. In conclusion, OCA administration during gestation had no apparent detrimental impact on maternal or fetal morphometry and improved fetal hypercholanemia. As high serum bile acid concentrations in ICP are associated with increased rates of adverse fetal outcomes, further investigations into the potential use of OCA during cholestatic gestation are warranted.
|
|
