Browsing by Subject "Bile acids"

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  • Hague, William M.; Callaway, Leonie; Chambers, Jennifer; Chappell, Lucy; Coat, Suzette; de Haan-Jebbink, Jiska; Dekker, Marloes; Dixon, Peter; Dodd, Jodie; Fuller, Maria; Gordijn, Sanne; Graham, Dorothy; Heikinheimo, Oskari; Hennessy, Annemarie; Kaaja, Risto; Khong, Teck Yee; Lampio, Laura; Louise, Jennie; Makris, Angela; Markus, Corey; Marschall, Hanns-Ulrich; Middleton, Philippa; Mol, Ben W.; Morris, Jonathan; Newnham, John P.; Ovadia, Caroline; Peek, Michael; Shand, Antonia; Stark, Michael; Thornton, Jim; Timonen, Susanna; Walker, Susan; Warrilow, David; Williamson, Catherine (2021)
    BackgroundSevere early onset (less than 34weeks gestation) intrahepatic cholestasis of pregnancy (ICP) affects 0.1% of pregnant women in Australia and is associated with a 3-fold increased risk of stillbirth, fetal hypoxia and compromise, spontaneous preterm birth, as well as increased frequencies of pre-eclampsia and gestational diabetes. ICP is often familial and overlaps with other cholestatic disorders.Treatment options for ICP are not well established, although there are limited data to support the use of ursodeoxycholic acid (UDCA) to relieve pruritus, the main symptom. Rifampicin, a widely used antibiotic including in pregnant women, is effective in reducing pruritus in non-pregnancy cholestasis and has been used as a supplement to UDCA in severe ICP. Many women with ICP are electively delivered preterm, although there are no randomised data to support this approach.MethodsWe have initiated an international multicentre randomised clinical trial to compare the clinical efficacy of rifampicin tablets (300mg bd) with that of UDCA tablets (up to 2000mg daily) in reducing pruritus in women with ICP, using visual pruritus scores as a measuring tool.DiscussionOur study will be the first to examine the outcomes of treatment specifically in the severe early onset form of ICP, comparing "standard" UDCA therapy with rifampicin, and so be able to provide for the first-time high-quality evidence for use of rifampicin in severe ICP. It will also allow an assessment of feasibility of a future trial to test whether elective early delivery in severe ICP is beneficial.Trial identifiersAustralian New Zealand Clinical Trials Registration Number (ANZCTR): 12618000332224p (29/08/2018). HREC No: HREC/18/WCHN/36.EudraCT number: 2018-004011-44.IRAS: 272398.NHMRC registration: APP1152418 and APP117853.
  • Hague, William M; Callaway, Leonie; Chambers, Jennifer; Chappell, Lucy; Coat, Suzette; de Haan-Jebbink, Jiska; Dekker, Marloes; Dixon, Peter; Dodd, Jodie; Fuller, Maria; Gordijn, Sanne; Graham, Dorothy; Heikinheimo, Oskari; Hennessy, Annemarie; Kaaja, Risto; Khong, Teck Y; Lampio, Laura; Louise, Jennie; Makris, Angela; Markus, Corey; Marschall, Hanns-Ulrich; Middleton, Philippa; Mol, Ben W; Morris, Jonathan; Newnham, John P; Ovadia, Caroline; Peek, Michael; Shand, Antonia; Stark, Michael; Thornton, Jim; Timonen, Susanna; Walker, Susan; Warrilow, David; Williamson, Catherine (BioMed Central, 2021)
    Abstract Background Severe early onset (less than 34 weeks gestation) intrahepatic cholestasis of pregnancy (ICP) affects 0.1% of pregnant women in Australia and is associated with a 3-fold increased risk of stillbirth, fetal hypoxia and compromise, spontaneous preterm birth, as well as increased frequencies of pre-eclampsia and gestational diabetes. ICP is often familial and overlaps with other cholestatic disorders. Treatment options for ICP are not well established, although there are limited data to support the use of ursodeoxycholic acid (UDCA) to relieve pruritus, the main symptom. Rifampicin, a widely used antibiotic including in pregnant women, is effective in reducing pruritus in non-pregnancy cholestasis and has been used as a supplement to UDCA in severe ICP. Many women with ICP are electively delivered preterm, although there are no randomised data to support this approach. Methods We have initiated an international multicentre randomised clinical trial to compare the clinical efficacy of rifampicin tablets (300 mg bd) with that of UDCA tablets (up to 2000 mg daily) in reducing pruritus in women with ICP, using visual pruritus scores as a measuring tool. Discussion Our study will be the first to examine the outcomes of treatment specifically in the severe early onset form of ICP, comparing “standard” UDCA therapy with rifampicin, and so be able to provide for the first-time high-quality evidence for use of rifampicin in severe ICP. It will also allow an assessment of feasibility of a future trial to test whether elective early delivery in severe ICP is beneficial. Trial identifiers Australian New Zealand Clinical Trials Registration Number (ANZCTR): 12618000332224p (29/08/2018). HREC No: HREC/18/WCHN/36. EudraCT number: 2018–004011-44. IRAS: 272398. NHMRC registration: APP1152418 and APP117853.
  • Toresson, L.; Steiner, J. M; Suchodolski, J. S (BioMed Central, 2021)
    Abstract Background In people, bile acid diarrhoea is a prevalent complication of Crohn’s disease and diarrhoea-associated irritable bowel syndrome. Affected patients typically respond to bile acid sequestrants, such as cholestyramine, but human gastroenterologists often fail to recognize bile acid diarrhoea. Consequently, bile acid diarrhoea is regarded as an underrecognized and undertreated condition in human medicine. Due to lack of diagnostic tools, clinical response to bile acid sequestrants is often used to confirm a diagnosis of bile acid diarrhoea in people. Several recent studies have shown that bile acid dysmetabolism also occurs in dogs with chronic enteropathies. It has further been shown that dogs with chronic enteropathies have significantly decreased expression of a bile acid transport protein in the ileum compared to healthy dogs, which correlates with faecal bile acid dysmetabolism. Consequently, in spite of the lack of reports in the literature, bile acid diarrhoea is likely to exist in dogs as well. Case descriptions Two dogs, an 8-year old Rottweiler and a 4.5-year old Siberian Husky were evaluated for chronic watery diarrhoea. Neither dog responded to dietary trials, probiotics, cyclosporine, faecal microbial transplantations or metronidazole. One of the dogs responded to high daily doses of corticosteroids, which were however associated with unacceptable side effects. The other dog was refractory to all standard treatment protocols, including cyclosporine and corticosteroids. Since none of the dogs responded satisfactorily to standard treatment or modulation of the intestinal microbiome, a suspicion of possible bile acid diarrhoea was raised. Treatment with cholestyramine, a bile acid sequestrant was initiated and resulted in marked improvement of faecal consistency, frequency of defecation and activity level in both dogs. Conclusion This report presents two dogs with presumed bile acid diarrhoea that were successfully treated with cholestyramine. Therefore, bile acid diarrhoea should be considered as a possible diagnosis in dogs with treatment-refractory chronic diarrhoea.
  • Jäämaa, Salla (Helsingfors universitet, 2010)
    Lung transplantation (LTx) is a generally accepted therapy for end-stage lung patients meeting the international criterias. Chronic dysfunction of the allograft, called Brochiolitis Obliterans Syndrome (BOS), is the most important complication limiting the long term survival of these patients. Known risk factors for developing BOS are episodes of acute rejection, CMV-pneumonitis and HLA-immunization. Other risk factors have also been suggested, as one of them gastroesophageal reflux disease (GERD) and the possible microaspiration caused by it. In this study we followed during one year 15 patients who underwent a bilateral LTx in Helsinki University Central Hospital. Our aim was to find out if it is possible to determine bile acids from lung allograft recipients' bronchoalveolar lavage fluid (BALF) by using a commercially available kit and thus possibly find a useful method to verify the microaspiration in these patients. Our study demonstrates that most patients do have bile acids in their BALF samples during the first year after LTx and that this does not correlate with the reflux symptoms experienced by the patients. We were unable to show correlation between the bile acids in BALF and BOS developed by some patients, but our results indicate that BOS is preceded by repeated episodes of BALF neutrophilia.
  • Sinisalu, Lisanna; Sen, Partho; Salihovic, Samira; Virtanen, Suvi M.; Hyöty, Heikki; Ilonen, Jorma; Toppari, Jorma; Veijola, Riitta; Oresic, Matej; Knip, Mikael; Hyötyläinen, Tuulia (2020)
    Celiac disease (CD) is a systemic immune-mediated disorder with increased frequency in the developed countries over the last decades implicating the potential causal role of various environmental triggers in addition to gluten. Herein, we apply determination of perfluorinated alkyl substances (PFAS) and combine the results with the determination of bile acids (BAs) and molecular lipids, with the aim to elucidate the impact of prenatal exposure on risk of progression to CD in a prospective series of children prior the first exposure to gluten (at birth and at 3 months of age). Here we analyzed PFAS, BAs and lipidomic profiles in 66 plasma samples at birth and at 3 months of age in the Type 1 Diabetes Prediction and Prevention (DIPP) study (n = 17 progressors to CD, n = 16 healthy controls, HCs). Plasma PFAS levels showed a significant inverse association with the age of CD diagnosis in infants who later progressed to the disease. Associations between BAs and triacylglycerols (TGs) showed different patterns already at birth in CD pmgressors, indicative of different absorption of lipids in these infants. In conclusion, PFAS exposure may modulate lipid and BA metabolism, and the impact is different in the infants who develop CD later in life, in comparison to HCs. The results indicate more efficient uptake of PFAS in such infants. Higher PFAS exposure during prenatal and early life may accelerate the progression to CD in the genetically predisposed children.
  • Stenman, Lotta K.; Holma, Reetta; Korpela, Riitta (2012)
  • McGlinchey, Aidan; Sinioja, Tim; Lamichhane, Santosh; Sen, Partho; Bodin, Johanna; Siljander, Heli; Dickens, Alex M.; Geng, Dawei; Carlsson, Cecilia; Duberg, Daniel; Ilonen, Jorma; Virtanen, Suvi M.; Dirven, Hubert; Berntsen, Hanne Friis; Zimmer, Karin; Nygaard, Unni C.; Oresic, Matej; Knip, Mikael; Hyötyläinen, Tuulia (2020)
    In the last decade, increasing incidence of type 1 diabetes (T1D) stabilized in Finland, a phenomenon that coincides with tighter regulation of perfluoroalkyl substances (PFAS). Here, we quantified PFAS to examine their effects, during pregnancy, on lipid and immune-related markers of T1D risk in children. In a mother-infant cohort (264 dyads), high PFAS exposure during pregnancy associated with decreased cord serum phospholipids and progression to T1D-associated islet autoantibodies in the offspring. This PFAS-lipid association appears exacerbated by increased human leukocyte antigen-conferred risk of T1D in infants. Exposure to a single PFAS compound or a mixture of organic pollutants in non-obese diabetic mice resulted in a lipid profile characterized by a similar decrease in phospholipids, a marked increase of lithocholic acid, and accelerated insulitis. Our findings suggest that PFAS exposure during pregnancy contributes to risk and pathogenesis of T1D in offspring.