Genetic Contributors and Modifiers of Biliary Atresia

To date, the etiology and pathogenic underpinning of the progression of the most prevalent serious neonatal liver disease, biliary atresia, remains elusive. This disease presents as an aggressive form of neonatal cholestasis characterized by the destruction and obliteration of the extrahepatic bile ducts within the first few weeks of life and a rapid progression of biliary fibrosis, likely due to unremitting cholestasis and retention of biliary constituents including bile acids. In ∼5% of patients, biliary atresia is associated with laterality features, suggesting a genetic underpinning to a disease that begins soon after birth. However, biliary atresia does not occur within families and twins are discordant, indicating an absence of strict mendelian inheritance. Despite this, genes related to bile duct dysmorphogenesis/ciliopathies overlapping with features of biliary atresia in both humans and nonhuman model systems have been proposed. Taken together, strict genetic etiologies leading to a common pathway of a neonatal cholangiopathy resulting in biliary atresia remain elusive. Contributions from fibrogenesis- and inflammation-based studies suggest that early engagement of these pathways contributes to disease progression, but a recent double-blind study did not suggest any benefit from early use of corticosteroids. However, there are genetic contributions to the adaptation and response to cholangiopathies and cholestasis that may be present in certain populations that likely impact upon the response to hepatoportoenterostomy and subsequent biliary tract function. Studies utilizing next generation sequencing technologies (e.g., exome analysis) are ongoing in several laboratories around the world; they are expected to provide insights into genetic contributions to biliary atresia outcomes. Altogether, combinations of exome sequencing and large population studies are expected to reveal causative and modifying genes relevant to patients with biliary atresia as a means to provide therapeutic targets and potential opportunities for genetic screening.

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Double-blind study of metaxalone; use as skeletal-muscle relaxant

JAMA ◽

10.1001/jama.195.6.479 ◽

1966 ◽

Vol 195 (6) ◽

pp. 479-480 ◽

Cited By ~ 3

Author(s):

S. Diamond

Keyword(s):

Skeletal Muscle ◽

Muscle Relaxant ◽

Blind Study ◽

Double Blind Study ◽

Double Blind ◽

Skeletal Muscle Relaxant

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Discontinuation of antistreptococcal prophylaxis. A double-blind study in rheumatic patients free of heart disease

JAMA ◽

10.1001/jama.197.12.949 ◽

1966 ◽

Vol 197 (12) ◽

pp. 949-952 ◽

Cited By ~ 3

Author(s):

A. R. Feinstein

Keyword(s):

Heart Disease ◽

Blind Study ◽

Double Blind Study ◽

Double Blind ◽

Rheumatic Patients

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Effect of pomegranate fruit supplementation on performance and various markers in athletes and active subjects: a systematic review

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831/a000601 ◽

2019 ◽

pp. 1-15

Author(s):

Alicja Urbaniak ◽

Anna Skarpańska-Stejnborn

Keyword(s):

Vessel Diameter ◽

Whole Body ◽

Double Blind Study ◽

Double Blind ◽

Physically Active ◽

Highly Active ◽

Body Strength ◽

Rate Of Increase ◽

Study Designs ◽

Pomegranate Fruit

Abstract. The aim of the study was to review recent findings on the use of POM supplements in athletes of various disciplines and physically active participants. Eleven articles published between 2010 and 2018 were included, where the total number of investigated subjects was 176. Male participants constituted the majority of the group (n = 155), as compared to females (n = 21). 45% of research described was conducted on athletes, whereas the remaining studies were based on highly active participants. Randomised, crossover, double-blind study designs constituted the majority of the experimental designs used. POM supplementation varied in terms of form (pills/juice), dosage (50 ml–500 ml) and time of intervention (7 days–2 months) between studies. Among the reviewed articles, POM supplementation had an effect on the improvement of the following: whole body strength; feeling of vitality; acute and delayed muscle fatigue and soreness; increase in vessel diameter; blood flow and serum level of TAC; reduction in the rate of increase for HR, SBP, CK and LDH; support in the recovery of post-training CK, LDH, CRP and ASAT to their baseline levels; reduction of MMP2, MMP9, hsCRP and MDA; and increased activity of antioxidant enzymes (glutathione peroxidase and superoxide dismutase). In the majority of reviewed articles POM supplementation had a positive effect on a variety of parameters studied and the authors recommended it as a supplement for athletes and physically active bodies.

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Review for "Short-term glucocorticoid treatment reduces circulating sclerostin concentrations in healthy young men: a randomized, placebo-controlled, double-blind study"

10.1002/jbm4.10341/v1/review1 ◽

2019 ◽

Author(s):

Davide Gatti

Keyword(s):

Young Men ◽

Blind Study ◽

Double Blind Study ◽

Short Term ◽

Double Blind ◽

Glucocorticoid Treatment

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Metformin Decreases the High Plasminogen Activator Inhibition Capacity, Plasma Insulin and Triglyceride Levels in Non-Diabetic Obese Subjects

Thrombosis and Haemostasis ◽

10.1055/s-0038-1651126 ◽

1987 ◽

Vol 57 (03) ◽

pp. 326-328 ◽

Cited By ~ 118

Author(s):

Ph Vague ◽

I Juhan-Vague ◽

M C Alessi ◽

C Badier ◽

J Valadier

Keyword(s):

Plasminogen Activator ◽

Fibrinolytic Activity ◽

Plasma Insulin ◽

Normal Glucose Tolerance ◽

Double Blind Study ◽

Obese Women ◽

Double Blind ◽

Normal Glucose ◽

Plasma Insulin Levels ◽

Obese Subjects

SummaryWe have previously observed a positive correlation between Plasminogen Activator Inhibition capacity (PA Inhibition), Body Mass Index (BMI) and plasma insulin levels in a population of non diabetic subjects. The anti diabetic biguanide Metformin which decreases insulin resistance has been reported to increase the blood fibrinolytic activity. Therefore we have studied the effect of Metformin on PA Inhibition levels in obese subjects with normal glucose tolerance. Eighteen obese women (O) (BMI: 31.4 ± 1.13, m ± S.E.M.) were compared to age matched controls (C) (BMI: 20.2 ± 0.8) and randomized to a 15 days treatment by Metformin (M) (1.7 g/day) or placebo (P) in a double blind study while on a weight maintaining diet. O compared to C had higher levels (m ± S.E.M.) of PA Inhibition (9 ± 1.8 IU/ml, versus 2.88 ± 0.29 p <0.01), lower euglobulin fibrinolytic activity (EFA) (4.95 ±1.17 mm versus 9 ± 0.29 p <0.05), higher plasma insulin (24.1 ±2.1. uU/ml), versus 12 ± 1 p <0.01) and triglyceride (1.32 ± 0.16 mmol/1, versus 0.8 ± 0.08 p <0.05). After 15 days of treatment, in group M a significant decrease in PA Inhibition (5.51 ± 1.4, versus 9.48 ±2.1 p <0.05) in plasma insulin (18.5 ±0.1, versus 24.5 ± 3.5, p <0.05) and plasma triglyceride (1.08 ± 0.1, versus 1.47 ± 0.3 p <0.05) and an increase in EFA (6.50 ± 0.28, versus 5.25 ± 0.35 p <0.05) were observed. No significant variation was observed in group P.

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The Effect of Warfarin Sodium on the Duration of Platelet Aggregation

Thrombosis and Haemostasis ◽

10.1055/s-0038-1655087 ◽

1967 ◽

Vol 18 (03/04) ◽

pp. 766-778 ◽

Cited By ~ 2

Author(s):

H. J Knieriem ◽

A. B Chandler

Keyword(s):

Platelet Count ◽

Placebo Group ◽

Platelet Aggregation ◽

Prothrombin Time ◽

Platelet Rich Plasma ◽

Healthy Adults ◽

Double Blind Study ◽

Double Blind ◽

Warfarin Sodium

SummaryThe effect of the administration of warfarin sodium (Coumadin®) on the duration of platelet aggregation in vitro was studied. Coumadin was given for 4 consecutive days to 10 healthy adults who were followed over a period of 9 days. The duration of adenosine diphosphate-induced platelet aggregation in platelet-rich plasma, the prothrombin time, and the platelet count of platelet-rich plasma were measured. Four other healthy adults received placebos and participated in a double-blind study with those receiving Coumadin.Although administration of Coumadin caused a prolongation of the prothrombin time to 2 or 21/2 times the normal value, a decrease in the duration of platelet aggregation was not observed. In most individuals who received Coumadin an increase in the duration of platelet aggregation occurred. The effect of Coumadin on platelet aggregation was not consistently related to the prothrombin time or to the platelet count. In the placebo group there was a distinct relation between the duration of platelet aggregation and the platelet count in platelet-rich plasma.The mean increase in the duration of platelet aggregation when compared to the control value before medication with Coumadin was 37.7%. In the placebo group there was a mean increase of 8.4%. The difference between the two groups is significant (p <0.001). Increased duration of platelet aggregation also occurred in two individuals who received Coumadin over a period of 10 and 16 days respectively.

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