Search

Charcot-Marie Tooth type 2B (CMT2B) is a rare inherited peripheral neuropathy caused by five missense mutations in the RAB7A gene, which encodes a small GTPase of the RAB family. Currently, no cure is available for this disease. In this study, we approached the disease by comparing the lipid metabolism of CMT2B-derived fibroblasts to that of healthy controls. We found that CMT2B cells showed increased monounsaturated fatty acid level and increased expression of key enzymes of monounsaturated and polyunsaturated fatty acid synthesis. Moreover, in CMT2B cells a higher expression of acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS), key enzymes of de novo fatty acid synthesis, with a concomitantly increased [1- 14 C]acetate incorporation into fatty acids, was observed. The expression of diacylglycerol acyltransferase 2, a rate-limiting enzyme in triacylglycerol synthesis, as well as triacylglycerol levels were increased in CMT2B compared to control cells. In addition, as RAB7A controls lipid droplet breakdown and lipid droplet dynamics have been linked to diseases, we analyzed these organelles and showed that in CMT2B cells there is a strong accumulation of lipid droplets compared to control cells, thus reinforcing our data on abnormal lipid metabolism in CMT2B. Furthermore, we demonstrated that ACC and FAS expression levels changed upon RAB7 silencing or overexpression in HeLa cells, thus suggesting that metabolic modifications observed in CMT2B-derived fibroblasts can be, at least in part, related to RAB7 mutations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

In an abattoir survey of the consecutive series of 206 sheep at a local slaughterhouse, gallstones (concretions with a diameter equal to or greater than 1 mm) were found in the gall bladder of 24 animals. There were stones in 19 out of 146 adult sheep and in 5 out of 60 lambs, with the higher frequency in the male sex in both groups. Qualitative analysis of the stones showed that all of them were pigment (bilirubin) stones. There was no statistically significant difference (paired t test, P greater than 0.05) between the amounts of biliary cholesterol, phospholipids, bile acids and total and indirect bilirubin in 12 sheep with gallstones and 12 control sheep without gallstones, paired for age, sex and day of slaughter.

17 beta-Estradiol was administered for 4 weeks percutaneously (5 mg/day) and, after a 6-week period to allow the drug to wash out, orally (2 mg/day) to a postmenopausal woman in whom a Kerr tube had been placed because of an iatrogenic lesion of the common bile duct. After both methods of administration, there was an increase in the biliary cholesterol concentration, but after oral administration, bile flow also increased and cholesterol crystals appeared in the bile. The percutaneous method of estradiol administration in postmenopausal women seems to be less dangerous for the biliary tract.