Impact of citrulline substitution on clinical outcome after liver transplantation in carbamoyl phosphate synthetase 1 and ornithine transcarbamylase deficiency.

Carbamoyl phosphate synthetase 1 (CPS1) and ornithine transcarbamylase (OTC) deficiencies are rare urea cycle disorders, which can lead to life-threatening hyperammonemia. Liver transplantation (LT) provides a cure and offers an alternative to medical treatment and life-long dietary restrictions with permanent impending risk of hyperammonemia. Nevertheless, in most patients, metabolic aberrations persist after LT, especially low plasma citrulline levels, with questionable clinical impact. So far, little is known about these alterations and there is no consensus, whether l-citrulline substitution after LT improves patients' symptoms and outcomes. In this multicentre, retrospective, observational study of 24 patients who underwent LT for CPS1 (n = 11) or OTC (n = 13) deficiency, 25% did not receive l-citrulline or arginine substitution. Correlation analysis revealed no correlation between substitution dosage and citrulline levels (CPS1, p = 0.8 and OTC, p = 1). Arginine levels after liver transplantation were normal after LT independent of citrulline substitution. Native liver survival had no impact on mental impairment (p = 0.67). Regression analysis showed no correlation between l-citrulline substitution and failure to thrive (p = 0.611) or neurological outcome (p = 0.701). Peak ammonia had a significant effect on mental impairment (p = 0.017). Peak plasma ammonia levels correlate with mental impairment after LT in CPS1 and OTC deficiency. Growth and intellectual impairment after LT are not significantly associated with l-citrulline substitution.

Effects of dietary seaweed on obesity-related metabolic status: a systematic review and meta-analysis of randomized controlled trials.

CONTEXT: Seaweed is a promising source of anti-obesity agents, including polysaccharides, proteins, polyphenols, carotenoids, and n-3 long-chain polyunsaturated fatty acids. The anti-obesity effects of such compounds may be due to several mechanisms, including inhibition of lipid absorption and metabolism, effect on satiety, and inhibition of adipocyte differentiation. OBJECTIVE: The aim of this study was to assess the evidence from human randomized controlled trials for the effects of seaweed on body-weight status as well as lipid and nonlipid parameters in adults with overweight and obesity. DATA SOURCES: Four databases-Medline, Scopus, Web of Science, and Cochrane Library-were searched from December 2022 to June 2023 using the following key words: Seaweed OR fucoxanthin OR alginates OR fucoidans OR phlorotannin's OR macroalgae OR marine algae AND obesity OR overweight OR BMI OR body mass index. DATA EXTRACTION: Eleven interventional studies (10 parallel and 1 crossover) were extracted. DATA ANALYSIS: Meta-analysis showed a significant effect, favoring the intervention group for BMI (body mass index) (standardized mean difference [SMD]: -0.40; 95% CI: -0.65 to -0.16 kg/m2; P = 0.0013) and percentage of fat mass (SMD: -1.48; 95% CI: -2.66% to -0.30%, P = 0.0138). The results were seen when refined or extracted brown seaweed (BMI) or only refined brown seaweed (% fat mass) were administered to participants for at least 8 weeks. Moreover, a significant overall effect of seaweed supplementation on total cholesterol (SMD: -7.72; 95% CI: -12.49 to -2.95 mg/dL; P = 0.0015) and low-density-lipoprotein cholesterol (SMD: -7.33; 95% CI: -11.64 to -3.02 mg/dL; P < 0.001) was noted. Any significant effects of seaweed on glucose metabolism were not shown. CONCLUSION: Edible seaweed supplementation shows potential for managing obesity and disorders of the blood lipid profile when administered to participants for at least 8 weeks. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42022378484 (www.crd.york.ac.uk/PROSPERO).

Thrombopoietin exerts a neuroprotective effect by inhibiting the suppression of neuronal proliferation and axonal outgrowth in intrauterine growth restriction rats.

Chronic hypoxia in utero causes intrauterine growth restriction (IUGR) of the fetus. IUGR infants are known to be at higher risk for neurodevelopmental disorders, but the mechanism is unclear. In this study, we analyzed the structure of the cerebral cortex using IUGR model rats generated through a reduced uterine perfusion pressure operation. IUGR rats exhibited thinner cerebral white matter and enlarged lateral ventricles compared with control rats. Expression of neuron cell markers, Satb2, microtubule-associated protein (MAP)-2, α-tubulin, and nestin was reduced in IUGR rats, indicating that neurons were diminished at various developmental stages in IUGR rats, from neural stem cells to mature neurons. However, there was no increase in apoptosis in IUGR rats. Cells positive for Ki67, a marker of cell proliferation, were reduced in neurons and all glial cells of IUGR rats. In primary neuron cultures, axonal elongation was impaired under hypoxic culture conditions mimicking the intrauterine environment of IUGR infants. Thus, in IUGR rats, chronic hypoxia in utero suppresses the proliferation of neurons and glial cells as well as axonal elongation, resulting in cortical thinning and enlarged lateral ventricles. Thrombopoietin (TPO), a platelet growth factor, inhibited the decrease in neuron number and promoted axon elongation in primary neurons under hypoxic conditions. Intraperitoneal administration of TPO to IUGR rats resulted in increases in the number of NeuN-positive cells and the area coverage of Satb2. In conclusion, suppression of neuronal proliferation and axonal outgrowth in IUGR rats resulted in cortical thinning and enlargement of lateral ventricles. TPO administration might be a novel therapeutic strategy for treating brain dysmaturation in IUGR infants.