L-Ornithine L-Aspartate: Multimodal Therapeutic Agent for Hyperammonemia and Hepatic Encephalopathy in Cirrhosis
Bibliographic record
Abstract
L-ornithine L-aspartate (LOLA) is a 1:1 stable salt of naturally-occurring amino acids L-ornithine and L-aspartic acid.Following oral administration, LOLA is rapidly absorbed dependent on the Na + ion gradient.The elimination half-life is estimated to be in the 30-45 min range with bioavailability of 82.2%.LOLA has the proven capacity to cause lowering of blood ammonia and it does so as a result of multiple established mechanisms.Being a urea cycle intermediate and, more specifically, an activator of carbomyl phosphate synthetase, L-ornithine stimulates ammonia removal as urea by periportal hepatocytes.Both L-ornithine and L-aspartate are substrates for transamination reactions resulting in formation of glutamate, the obligate substrate for glutamine synthetase located in perivenous hepatocytes, skeletal muscle and brain.Increases of brain glutamine correlate with severity of Hepatic Encephalopathy (HE) in patients with cirrhosis.In cirrhosis, the normal pattern of inter-organ trafficking is modified and skeletal muscle replaces the liver as the major ammonia-removing organ.Muscle wasting (sarcopenia) occurs in cirrhosis as a result of exposure to ammonia and this seriously limits its ammonia-lowering capacity leading to a vicious cycle and worsening of hyperammonemia.Trials demonstrate that treatment with LOLA improves muscle function in patients with cirrhosis.There is evidence to suggest that LOLA also has direct hepatoprotective actions in these patients via mechanisms related to the production of antioxidants and the synthesis of nitric oxide leading to improved hepatic microcirculation.Over 20 randomized controlled trials together with systematic reviews and meta-analyses have demonstrated that LOLA is effective for the prevention and treatment of HE in cirrhosis where improvements in mental state occurred as a consequence of the lowering of circulating ammonia.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".