scholarly journals Extended Abstract: Deficiency of Sodium Taurocholate Cotransporting Polypeptide (SLC10A1): A New Inborn Error of Metabolism with an Attenuated Phenotype

2017 ◽  
Vol 35 (3) ◽  
pp. 259-260 ◽  
Author(s):  
Frédéric M. Vaz ◽  
Hidde H. Huidekoper ◽  
Coen C. Paulusma
Keyword(s):  
Bile Salts ◽  
Clinical Presentation ◽  
Enterohepatic Circulation ◽  
Sodium Taurocholate ◽  
Elevated Plasma ◽  
Mild Phenotype ◽  
Functional Studies ◽  
Conjugated Bile Salts

We present the first patient with a defect in the Na+-taurocholate cotransporting polypeptide SLC10A1 (NTCP), which plays a key role in the enterohepatic circulation of bile salts. The clinical presentation of the child was mild and the child showed no signs of liver dysfunction or pruritus despite extremely elevated plasma bile salt levels (>100-fold upper-limit of normal). A homozygous point mutation was found in the SLC10A1 gene (resulting in amino acid change R252H) and functional studies confirmed the pathogenicity of the mutation. This confirms the role of NTCP as the major transporter of conjugated bile salts into the liver as part of the enterohepatic circulation and shows that other transporters partly can take over its function, resulting in a relatively mild phenotype. This work was published previously in [Vaz et al.: Hepatology 2015;61:260-267] and supplemented with some follow-up information of the patient.

scholarly journals FRI0212 THE ROLE OF AGE ON THE CLINICAL PRESENTATION AND RELAPSE RATES IN A LARGE COHORT OF 720 PATIENTS WITH GIANT CELL ARTERITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 689.1-690
Author(s):  
S. Monti ◽  
L. Dagna ◽  
C. Campochiaro ◽  
A. Tomelleri ◽  
G. Zanframundo ◽  
...  
Keyword(s):  
Giant Cell Arteritis ◽  
Giant Cell ◽  
Relapse Rate ◽  
Clinical Presentation ◽  
Age Groups ◽  
Age At Diagnosis ◽  
First Relapse ◽  
Time To Relapse

Background:Giant cell arteritis (GCA) is the most frequent systemic vasculitis after the age of 50 years old. Recent interest in the processes of immune and vascular aging have been proposed as a disease risk factor. Data on the impact of age at diagnosis of GCA on the clinical course of the disease are scarceObjectives:To assess the role of age at diagnosis of GCA on the risk and time to relapseMethods:Centres participating in the Italian Society of Rheumatology Vasculitis Study Group retrospectively enrolled patients with a diagnosis of GCA until December 2019. The cohort was divided in tertiles according to age at diagnosis (≤ 72; 73-79; > 79 years old). Negative binomial regression was used to assess the relapse rate according to age groups, and Cox regression for time to first relapse.Results:Of 720 patients enrolled in 14 Italian reference centres, 711 had complete follow-up data (female 50%; mean age 75±7). Median follow-up duration was 34 months (IQR 16;70). Patients in the older group at diagnosis (> 79 years) had more frequent visual loss compared to the 73-79 and ≤ 72 age groups (31% vs 20% vs 7%; p<0.001), but lower rates of general symptoms (56% vs 70% vs 77%; p<0.001). Large-vessel (LV)-GCA was less frequent in the older group (18% vs 22% vs 43%; p<0.001). At least one relapse occurred in 47% of patients. Median time to relapse was 12 months (IQR 6;23). Age did not influence the rate of relapses [18 per 100 persons/years (95%CI 15;21) vs 19 (95% CI 17;22) vs 19 (95%CI 17;22)], nor the time to first relapse (Figure 1). LV-GCA, presentation with significantly elevated c-reactive protein (> 50 mg/L) and general symptoms were independent predictors of relapse.Conclusion:Age at diagnosis of GCA influenced the clinical presentation and risk of ischaemic complications, but did not affect the relapse rate during follow-up. LV-GCA occurred more frequently in younger patients and was an independent predictor of relapse risk, highlighting the need for a correct characterization of the clinical subtype at the early stages of disease.Disclosure of Interests:Sara Monti: None declared, Lorenzo Dagna Grant/research support from: Abbvie, BMS, Celgene, Janssen, MSD, Mundipharma Pharmaceuticals, Novartis, Pfizer, Roche, SG, SOBI, Consultant of: Abbvie, Amgen, Biogen, BMS, Celltrion, Novartis, Pfizer, Roche, SG, and SOBI, Corrado Campochiaro Speakers bureau: Novartis, Pfizer, Roche, GSK, SOBI, Alessandro Tomelleri: None declared, Giovanni Zanframundo: None declared, Catherine Klersy: None declared, Francesco Muratore: None declared, Luigi Boiardi: None declared, Roberto Padoan: None declared, Mara Felicetti: None declared, Franco Schiavon: None declared, Milena Bond: None declared, Alvise Berti: None declared, Roberto Bortolotti: None declared, Carlotta Nannini: None declared, Fabrizio Cantini: None declared, Alessandro Giollo: None declared, Edoardo Conticini: None declared, angelica gattamelata: None declared, Roberta Priori: None declared, Luca Quartuccio Consultant of: Abbvie, Bristol, Speakers bureau: Abbvie, Pfizer, Elena Treppo: None declared, Giacomo Emmi: None declared, Martina Finocchi: None declared, Giulia Cassone: None declared, Ariela Hoxha Speakers bureau: Celgene, UCB, Novartis, Sanofi, Werfen, Rosario Foti Consultant of: lilly, sanofi, MSD, Janssen, Abbvie, BMS, celgene, roche, Speakers bureau: lilly, sanofi, MSD, Janssen, Abbvie, BMS, celgene, roche, Michele Colaci: None declared, Roberto Caporali Consultant of: AbbVie; Gilead Sciences, Inc.; Lilly; Merck Sharp & Dohme; Celgene; Bristol-Myers Squibb; Pfizer; UCB, Speakers bureau: Abbvie; Bristol-Myers Squibb; Celgene; Lilly; Gilead Sciences, Inc; MSD; Pfizer; Roche; UCB, Carlo Salvarani: None declared, Carlomaurizio Montecucco: None declared

Effect of intestinal resection on bile salt absorption in dogs

1965 ◽  
Vol 208 (2) ◽  
pp. 363-369 ◽  
Author(s):  
M. R. Playoust ◽  
Leon Lack ◽  
I. M. Weiner
Keyword(s):  
Bile Salt ◽  
Bile Salts ◽  
Enterohepatic Circulation ◽  
Sodium Taurocholate ◽  
Intestinal Resection ◽  
High Fat ◽  
Salt Absorption ◽  
Complete Failure ◽  
Fat Meal

The efficiency of intestinal absorption of bile salts was evaluated by studying the rate of disappearance of radioactivity from the bile of dogs after the intravenous administration of sodium taurocholate-24-C14. Bile was sampled through an indwelling tube in the gall bladder. One day after a high-fat meal normal dogs retained 48% of the radioactivity; dogs with resection of the jejunum retained 48%, whereas those with resection of the ileum retained only 3% in the bile. This is consistent with previous observations that the ileum is the site of bile salt absorption in vitro and in anesthetized animals. Animals with resection of the ileum exhibited significant steatorrhea; however, three-fourths of the ingested fat was absorbed in spite of almost complete failure to absorb bile salts. This indicates that fat and bile salts are not normally absorbed together. Elimination of enterohepatic circulation of bile salts by resection of the ileum contributes to the observed steatorrhea.

Biliary Inter-Relationship between Phospholipid, Bilirubin and Taurocholate in the Anaesthetized Rat

1984 ◽  
Vol 67 (5) ◽  
pp. 499-504 ◽  
Author(s):  
J. J. García-Marín ◽  
A. Esteller
Keyword(s):  
Body Weight ◽  
Bile Flow ◽  
Bile Salts ◽  
Mixed Micelle ◽  
Enterohepatic Circulation ◽  
Important Determinant ◽  
Sodium Taurocholate ◽  
Micelle Formation ◽  
Mixed Micelle Formation ◽  
Anaesthetized Rat

1. The interference between biliary phospholipid and bilirubin secretion was investigated in rats with bile fistulae, under conditions of normal and maximal bilirubin secretion. The enterohepatic circulation of bile salts was interrupted and the animals received infusions of sodium taurocholate, a micelle-forming physiological bile salt. 2. Sodium taurocholate infusion (0.19 μmol min−1 100 g−1 body weight) induced an increase in bile flow and phospholipid secretion, while basal bilirubin secretion was not increased. 3. Bilirubin infusion (0.26 μmol min−1 100 g−1 body weight) induced a decrease in basal and taurocholate-stimulated phospholipid secretion. Biliary mixed micelle formation was presumably altered during bilirubin infusion, although bile taurocholate concentration, taurocholate secretion rate and bile flow were not modified. 4. When sodium taurocholate was infused during bilirubin-decreased phospholipid secretion, this secretion was restored but maximal biliary bilirubin secretion was not increased. 5. These results provide circumstantial evidence for the hypothesis that mixed micelle formation is not an important determinant of maximal bilirubin transport into bile.

scholarly journals The Role of COA6 in the Mitochondrial Copper Delivery Pathway to Cytochrome c Oxidase

Biomolecules ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. 125
Author(s):  
Abhinav B. Swaminathan ◽  
Vishal M. Gohil
Keyword(s):  
Cytochrome C ◽  
Cytochrome C Oxidase ◽  
Mitochondrial Respiratory Chain ◽  
Functional Studies ◽  
Evolutionarily Conserved ◽  
Human Disorders ◽  
The Stability ◽  
Copper Delivery

Copper is essential for the stability and activity of cytochrome c oxidase (CcO), the terminal enzyme of the mitochondrial respiratory chain. Copper is bound to COX1 and COX2, two core subunits of CcO, forming the CuB and CuA sites, respectively. Biogenesis of these two copper sites of CcO occurs separately and requires a number of evolutionarily conserved proteins that form the mitochondrial copper delivery pathway. Pathogenic mutations in some of the proteins of the copper delivery pathway, such as SCO1, SCO2, and COA6, have been shown to cause fatal infantile human disorders, highlighting the biomedical significance of understanding copper delivery mechanisms to CcO. While two decades of studies have provided a clearer picture regarding the biochemical roles of SCO1 and SCO2 proteins, some discrepancy exists regarding the function of COA6, the new member of this pathway. Initial genetic and biochemical studies have linked COA6 with copper delivery to COX2 and follow-up structural and functional studies have shown that it is specifically required for the biogenesis of the CuA site by acting as a disulfide reductase of SCO and COX2 proteins. Its role as a copper metallochaperone has also been proposed. Here, we critically review the recent literature regarding the molecular function of COA6 in CuA biogenesis.

Effect of cannabis consumption on characteristics and evolution of thromboangitis obliterans

VASA ◽  
2021 ◽  
pp. 1-5
Author(s):  
Guillaume Bergère ◽  
Claire Toquet ◽  
Clément Hoffmann ◽  
Luc Bressollette ◽  
Alizée Raimbeau ◽  
...  
Keyword(s):  
Clinical Characteristics ◽  
Clinical Presentation ◽  
Thromboangiitis Obliterans ◽  
Tobacco Exposure ◽  
Free Survival ◽  
Younger Age ◽  
Arterial Involvement ◽  
Cannabis Consumption

Summary: Background: Thromboangiitis obliterans (TAO) is a distal non atherosclerotic thrombotic vasculitis affecting tobacco smokers. The role of cannabis co-exposure remains controversial. The study aims to assess how cannabis consumption influences clinical presentation and outcome of TAO in tobacco smokers. Patients and methods: TAO patients, according to Papa’s criteria, were included in a retrospective bicentric study between the 1st January 2003 and the 1st march 2020. Clinical characteristics, arterial involvement at TAO diagnosis, vascular event and amputations during follow-up were analyzed according to cannabis consumption. Results: Seventy-three patients with TAO patients were included. Forty-five patients were in Tobacco group (T) and 28 in Tobacco and cannabis group (T&C). Tobacco exposure was less important in T&C group than in T group (19.4±11.3 vs 31.6±16.6 pack-years) (p=0.005) and patients in T&C group were younger at TAO diagnosis than in T group (p=0.008). Patients in T&C group presented more claudication (33.3% vs 8.9%, p=0.01) and less upper limbs resting ischemia (25.9% vs 51.1%, p=0.04) than patients in the T group. No differences were found between groups with regard to arterial distribution. Amputation rate for patients who had at least one major or minor amputation did not differ between T and T&C group (25% vs 14.8%, p=0.38). Conclusions: Cannabis consumption was associated with a younger age of TAO onset. However, it does not affect amputation-free survival, Tobacco exposure is less important in T&C patients; data of this bicentric study suggest that cannabis could be a cofactor of tobacco which accelerates TAO onset.

Sign in / Sign up

Export Citation Format

Share Document