Juan Jorge Silva

Ursodeoxycholic acid in the treatment of cholestasis of pregnancy: a randomized double-blind study controlled with placebo

BACKGROUND/AIMS Intense pruritus and the risk of stillbirths and premature deliveries justify the search for an effective pharmacologic treatment of intrahepatic cholestasis of pregnancy. This study was designed to test the efficacy of ursodeoxycholic acid in maternal pruritus, the biochemical abnormalities and the outcome of pregnancy, in patients with intrahepatic cholestasis of pregnancy of early onset. METHODS Pregnant patients hospitalized in a secondary case-referral center with intense pruritus and abnormal serum levels of bile salts and aminotransferases, detected before week 33 of pregnancy, were randomly assigned to receive ursodeoxycholic acid, 1 g per day orally, or an identical placebo, until delivery, in a double-blind study. A 3-week trial period was chosen to compare drug and placebo effects. The follow-up was extended for 3 months after delivery. RESULTS Twenty-four patients entered the trial; eight had deliveries before 2 weeks of treatment and one dropped out. The study was then completed in 15 patients: eight received ursodeoxycholic acid and seven placebo. No adverse effects were detected in the mothers or in their babies. After 3 weeks of treatment, patients receiving ursodeoxycholic acid (mean daily dose 16 mg/kg body weight) had a significant improvement in pruritus (p<0.02), in serum bilirubin (0.36+/-0.19 mg/dl (mean+/-SD) versus 0.95+/-0.48 in patients receiving placebo, p<0.01), in aspartate aminotransferase (52+/-42 IU/l vs 98+/-44, p<0.05) and in alanine aminotransferase (54+/-50 IU/l vs 229+/-154, p<0.01); serum total bile salts also tended to be lower in patients receiving ursodeoxycholic acid (26.3+/-33.7 micromol/l vs 55.0+/-44.8, p N.S.). Deliveries occurred at or near term in all mothers who received ursodeoxycholic acid (mean week of pregnancy: 38), while they occurred before week 36 of pregnancy in five patients who received placebo, including one stillbirth. All babies born alive had birth weights adequate for gestational age and they were thriving normally 3 months after delivery. CONCLUSIONS Ursodeoxycholic acid is effective and safe in patients with intrahepatic cholestasis of pregnancy of early onset, attenuating pruritus and correcting some biochemical abnormalities in the mothers. Relevant aspects of fetal outcome were also improved in patients receiving ursodeoxycholic acid compared to placebo.

Ursodeoxycholic acid in the treatment of intrahepatic cholestasis of pregnancy. A 12-year experience.

Abstract: Objective: To assess the efficacy of ursodeoxycholic acid (UDCA) in patients with intrahepatic cholestasis of pregnancy (ICP) and in the outcome of pregnancy.

Is a leaky gut involved in the pathogenesis of intrahepatic cholestasis of pregnancy

Increased gastrointestinal permeability has been demonstrated in several liver diseases. It may facilitate the absorption of gut‐derived endotoxin‐stimulating Kupffer cells to release proinflammatory cytokines or other potentially hepatotoxic compounds. We examined gastrointestinal permeability, plasma levels of anti‐lipopolysacharides (anti‐LPS), and four proinflammatory cytokines in 20 patients with intrahepatic cholestasis of pregnancy (ICP) compared with 22 normal pregnant and 29 non‐pregnant women. Urinary excretion of sucrose and the urinary lactulose/mannitol (L/M) ratio after a standard oral load were used to assess gastrointestinal permeability. Anti‐LPS (IgA, IgM, and IgG) were measured in peripheral blood by Human EndoCAb test kit; TNF‐α, IL‐1β, IL‐6, and IL‐10 by Quantikine HS human immunoassays. Sucrose urinary excretion was similar in the three groups, indicating normal gastric permeability. The urinary L/M ratio was significantly higher in ICP than in the other groups [median (interquartile range): 0.018% (0.011‐0.023) in ICP, 0.012% (0.009‐0.016) in normal pregnancies, and 0.009% (0.008‐0.012) in non‐pregnant women, P < .01]. No significant differences were found in anti‐LPS or cytokines plasma levels except slightly higher levels of IL‐6 in ICP patients than in non‐pregnant women (P < .05). Four of five women with abnormal urinary L/M ratio during ICP continued to show abnormalities in tests up to 2 years after delivery. In conclusion, an increased intestinal permeability was detected in ICP patients during and after pregnancy. A “leaky gut” may participate in the pathogenesis of ICP by enhancing the absorption of bacterial endotoxin and the enterohepatic circulation of cholestatic metabolites of sex hormones and bile salts. (HEPATOLOGY 2006;43:715–722.)

A high-speed tracking algorithm for dense granular media

Abstract Many fields of study, including medical imaging, granular physics, colloidal physics, and active matter, require the precise identification and tracking of particle-like objects in images. While many algorithms exist to track particles in diffuse conditions, these often perform poorly when particles are densely packed together—as in, for example, solid-like systems of granular materials. Incorrect particle identification can have significant effects on the calculation of physical quantities, which makes the development of more precise and faster tracking algorithms a worthwhile endeavor. In this work, we present a new tracking algorithm to identify particles in dense systems that is both highly accurate and fast. We demonstrate the efficacy of our approach by analyzing images of dense, solid-state granular media, where we achieve an identification error of 5% in the worst evaluated cases. Going further, we propose a parallelization strategy for our algorithm using a GPU, which results in a speedup of up to 10 × when compared to a sequential CPU implementation in C and up to 40 × when compared to the reference MATLAB library widely used for particle tracking. Our results extend the capabilities of state-of-the-art particle tracking methods by allowing fast, high-fidelity detection in dense media at high resolutions.