The enterohepatic circulation of bile acids (BAs) critically depends on absorption of BA in the terminal ileum and colon, which can be affected by inflammatory bowel disease (IBD). Diarrhea in IBD is ...believed to result in part from BA malabsorption (BAM). We explored whether IBD alters mRNA expression of key intestinal BA transporters, BA detoxifying systems, and nuclear receptors that regulate BA transport and detoxification. Using real-time polymerase chain reaction, mucosal biopsy specimens from the terminal ileum in Crohn's disease (CD) patients and from the descending colon in ulcerative colitis (UC) patients were assessed for mRNA expression. Levels were compared with healthy controls. The main ileal BA uptake transporter, the apical sodium dependent bile acid transporter, was downregulated in active CD and UC and in CD in remission. Other significant changes such as repression of breast cancer-related protein and sulphotransferase 2A1 were seen only during active disease. In UC, pancolitis (but not exclusively left-sided colitis) was associated with altered expression of major BA transporters multidrug resistance-associated protein 3 (MRP3), MRP4, multidrug resistance gene 1, organic solute transporter α/β and nuclear receptors (pregnane X receptor, vitamin D receptor) in the descending colon. UC pancolitis leads to broad changes and CD ileitis to selective changes in intestinal BA transporter expression. Early medical manipulation of intestinal BA transporters may help prevent BAM.
2-Adic point counting on K3 surfaces Elsenhans, Andreas-Stephan; Jahnel, Jörg
Research in number theory,
12/2022, Letnik:
8, Številka:
4
Journal Article
Recenzirano
Odprti dostop
This article reports on an approach to point counting on algebraic varieties over finite fields that is based on a detailed investigation of the 2-adic orthogonal group. Combining the new approach ...with a
p
-adic method, we count the number of points on some
K
3 surfaces over the field
F
p
, for all primes
p
<
10
8
.
We study the moduli space 𝓜̃ of marked cubic surfaces. By classical work of A. B. Coble, this has a compactification M̃, which is linearly acted upon by the group W(E6). M̃ is given as the ...intersection of 30 cubics in P9. For the morphism 𝓜̃ → P(1, 2, 3, 4, 5) forgetting the marking, followed by Clebsch's invariant map, we give explicit formulas, i.e., Clebsch's invariants are expressed in terms of Coble's irrational invariants. As an application, we give an affirmative answer to the inverse Galois problem for cubic surfaces over ℚ.
We report on our results concerning the distribution of the geometric Picard ranks of
K
3 surfaces under reduction modulo various primes. In the situation that
rk
Pic
S
K
¯
is even, we introduce a ...quadratic character, called the jump character, such that
rk
Pic
S
F
¯
p
>
rk
Pic
S
K
¯
for all good primes at which the character evaluates to
(
-
1
)
.
The Hepatology Committee of the European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) aims to educate pediatric gastroenterologists, members of ESPGHAN and professionals ...from other specialties promoting an exchange of clinical expertise in the field of pediatric hepatology. Herewith we have concentrated on detailing the recent advances in acute liver failure in infants and children.
The 2020 ESPGHAN monothematic three-day conference on pediatric hepatology disease, entitled "acute liver failure" (ALF), was organized in Athens, Greece. ALF is a devastating disease with high mortality and most cases remain undiagnosed. As knowledge in diagnosis and treatment of ALF in infants and children has increased in the past decades, the objective was to update physicians in the field with the latest research and developments in early recognition, curative therapies and intensive care management, imaging techniques and treatment paradigms in these age groups.
In the first session, the definition, epidemiology, various causes of ALF, in neonates and older children and recurrent ALF (RALF) were discussed. The second session was dedicated to new aspects of ALF management including hepatic encephalopathy (HE), coagulopathy, intensive care interventions, acute on chronic liver failure, and the role of imaging in treatment and prognosis. Oral presentations by experts in various fields are summarized highlighting key learning points.
The current report summarizes the major learning points from this meeting. It also identifies areas where there is gap of knowledge, thereby identifying the research agenda for the near future.
The Hepatology Committee of the European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) aims to educate pediatric gastroenterologists, members of ESPGHAN and professionals ...from other specialties promoting an exchange of clinical expertise in the field of pediatric hepatology.
The 2020 single topic ESPGHAN monothematic 3-day conference on pediatric liver disease, was organized in Athens, Greece and was entitled " Acute Liver Failure" (ALF). ALF is a devastating disease with high mortality and in a considerable fraction of patients, the cause remains unresolved. As knowledge in diagnosis and treatment of ALF in infants and children has increased in the past decades, the objective was to update physicians in the field with developments in medical therapy and indications for liver transplantation (LT) and to identify areas for future research in clinical and neurocognitive outcomes in ALF.
We recently reported the epidemiology, diagnosis, and initial intensive care management issues in separate manuscript. Herewith we report on the medical treatment, clinical lessons arising from pediatric studies, nutritional and renal replacement therapy (RRT), indications and contraindications for LT, neurocognitive outcomes, new techniques used as bridging to LT, and areas for future research. Oral presentations by experts in various fields are summarized highlighting key learning points.
The current report summarizes the current insights in medical treatment of pediatric ALF and the directions for future research.
Patients with repaired tetralogy of Fallot may develop chronic right ventricular dysfunction and hepatic congestion over time. We hypothesized that bile acid metabolism is altered in repaired ...tetralogy of Fallot patients and therefore sought to correlate right ventricular indices with serum bile acid levels.
Indexed right ventricular end diastolic volume, as assessed by cardiac magnetic-resonance imaging, was classified as <100ml/m2 (Group 1, n = 5), 100-150ml/m2 (Group 2, n = 18), and >150ml/m2 (Group 3, n = 6) in 29 patients with repaired tetralogy of Fallot. Pulmonary regurgitation fraction and right ventricular ejection fraction were calculated. The serum bile acid profile, including 15 species, in these patients was determined by liquid chromatography coupled with mass spectrometry.
Serum bile acid levels increased from Group 1 to Group 3 (2.5 ± 0.7; 4.1 ± 2.5; 6.0 ± 2.8 μmol/l, respectively) with significantly increased bile acid values in Group 3 compared to Group 1 (p≤0.05). In Group 3, but not in Group 1 and 2, a significant increase in glycine-conjugated bile acids was observed. Pulmonary regurgitation fraction increased (12 ± 1; 28 ± 16; 43 ± 3%, Groups 1-3, respectively) and right ventricular ejection fraction decreased (48.4 ± 6.4; 48.5 ± 6.5; 42.1 ± 5.3%, Groups 1-3, respectively) with rising indexed right ventricular end diastolic volume.
These preliminary results suggest that serum bile acid levels are positively correlated with indexed right ventricular end-diastolic volume in patients with repaired tetralogy of Fallot; however, this needs to be confirmed in a larger patient cohort.
Accurate analytical methods for bile acid (BA) analysis are important for clinical diagnosis in newborns, adolescents, and adults. Improvements in speed, sensitivity and simplicity enable BA ...profiling using high performance liquid chromatography (HPLC) together with electrospray ionization (ESI) and high-resolution mass spectrometry (HR-MS).
We present a method, validated in different species and tissues, enabling a highly sensitive quantitative determination (in a range of 0.24pmol/sample to 1000pmol/sample, corresponding to 0.024–100pmol on column) of up to 36 naturally occurring BAs from as little as 10μl of plasma or serum, 1ml of urine, or 10mg of dried stool. Chromatographic separation is achieved by HPLC using a C18 reversed phase column and a water/methanol gradient. After ESI, BAs are analyzed through HR-MS using orbitrap technology in full scan mode. 30 different BAs and the corresponding internal standards are separated and analyzed in a single run. Six additional BAs are evaluated in a second run using a pentafluorophenyl (PFP) stationary phase.
This method generates detailed human and rodent BA profiles in full scan mode and accurate mass with the advantage of remarkably low required sample volume.
•Synthesis of conjugated bile acids and internal standards•HPLC high resolution mass spectrometry in full scan mode•Bile acid profiles of neonates and adolescents including atypical (rodent) bile acids
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