Attenuating hyperammonemia preserves protein synthesis and muscle mass via restoration of perturbed metabolic pathways in bile duct-ligated rats.

Sarcopenia and hepatic encephalopathy (HE) are complications of chronic liver disease (CLD), which negatively impact clinical outcomes. Hyperammonemia is considered to be the central component in the pathogenesis of HE, however ammonia's toxic effects have also been shown to impinge on extracerebral organs including the muscle. Our aim was to investigate the effect of attenuating hyperammonemia with ornithine phenylacetate (OP) on muscle mass loss and associated molecular mechanisms in rats with CLD.

Progression of Spinal Cord Disease in Adult Men With Adrenoleukodystrophy.

This study presents the longest systematic prospective follow-up of spinal cord disease in adult male ALD patients to date. Standardized yearly quantitative data collection included scoring of the EDSS, SSPROM, 6-min walking test (6MWT), urological and quality of life questionnaires and vibration sense of the hallux. Progression rates were compared between patients with mild (EDSS ≤ 2.

The role of adipose and muscle tissue breakdown on interorgan energy substrate fluxes in a Pseudomonas aeruginosa induced sepsis model in female pigs.

Sepsis leads to an acute breakdown of muscle to support increased caloric and amino acid requirements. Little is known about the role of adipose and muscle tissue breakdown and intestinal metabolism in glucose substrate supply during the acute phase of sepsis. In a translational porcine model of sepsis, we explored the across organ net fluxes of gluconeogenic substrates.

Altered lipid profile and reduced neuronal support in human induced pluripotent stem cell-derived astrocytes from adrenoleukodystrophy patients.

X-linked adrenoleukodystrophy (ALD) is a peroxisomal disorder resulting from pathogenic variants in the ABCD1 gene that primarily affects the nervous system and is characterized by progressive axonal degeneration in the spinal cord and peripheral nerves and leukodystrophy. Dysfunction of peroxisomal very long-chain fatty acid (VLCFA) degradation has been implicated in ALD pathology, but the impact on astrocytes, which critically support neuronal function, remains poorly understood. Fibroblasts from four ALD patients were reprogrammed to generate human-induced pluripotent stem cells (hiPSC).

The clinical and biochemical effectiveness and safety of cholic acid treatment for bile acid synthesis defects: a systematic review.

Background: Bile acid synthesis defects (BASDs) can be severely disabling involving the liver and nervous system, potentially due to elevated levels of toxic C-bile acid intermediates. Cholic acid (CA) supplementation is hypothesized to decrease bile acid production, stimulate bile secretion and -flow, and slowing down disease progression. This systematic review assesses the clinical and biochemical effectiveness, and safety of CA in BASDs patients.