Effects of citrulline on pathophysiological models of brain ageing and Alzheimer's disease

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Ornithine Aminotransferase, an Important Glutamate-Metabolizing Enzyme at the Crossroads of Multiple Metabolic Pathways

Ornithine δ-aminotransferase (OAT, E.C. 2.6.1.13) catalyzes the transfer of the δ-amino group from ornithine (Orn) to α-ketoglutarate (aKG), yielding glutamate-5-semialdehyde and glutamate (Glu), and vice versa. In mammals, OAT is a mitochondrial enzyme, mainly located in the liver, intestine, brain, and kidney. In general, OAT serves to form glutamate from ornithine, with the notable exception of the intestine, where citrulline (Cit) or arginine (Arg) are end products. Its main function is to control the production of signaling molecules and mediators, such as Glu itself, Cit, GABA, and aliphatic polyamines. It is also involved in proline (Pro) synthesis. Deficiency in OAT causes gyrate atrophy, a rare but serious inherited disease, a further measure of the importance of this enzyme

Primary Cutaneous Mucinous Carcinoma Monitoring: A Role for CA15.3 and CEA?

Primary cutaneous mucinous carcinoma (PCMC) is a rare malignant skin adnexal tumor. Recurrences are most often localized, and long-term follow-up after complete surgery consists essentially of self-examination of skin. We report one case of metastatic PCMC with elevated levels of serum CEA and CA15.3. Because of the difficulty to differentiate PCMC and metastasis of mucinous breast cancer, the hypothesis of a metastasized breast cancer was ruled out. These tumor markers contributed to the monitoring of the metastatic disease. Since metastatic disease was diagnosed after several years of seeming complete remission, CEA and CA15.3 would likely have allowed the clinicians to detect the relapse earlier. Although the use of tumor biomarkers in PCMC is not rooted in clinical practice and not mentioned in guidelines, we suggest that CEA and CA15.3 could be of particular interest to monitor and detect early metastatic PCMC

Serum Leptin Levels, Nutritional Status, and the Risk of Healthcare-Associated Infections in Hospitalized Older Adults

We aimed to determine whether serum leptin levels are predictive of the occurrence of healthcare-associated infections (HAIs) in hospitalized older patients. In a prospective cohort, 232 patients had available data for leptin and were monitored for HAIs for 3 months. Admission data included comorbidities, invasive procedures, the Mini Nutritional Assessment (MNA), BMI, leptin, albumin and C-reactive protein levels, and CD4 and CD8 T-cell counts. Multivariate logistic regression modelling was used to identify predictors of HAIs. Of the 232 patients (median age: 84.8; females: 72.4%), 89 (38.4%) experienced HAIs. The leptin level was associated with the BMI (p < 0.0001) and MNA (p < 0.0001) categories. Women who experienced HAIs had significantly lower leptin levels than those who did not (5.9 μg/L (2.6–17.7) and 11.8 (4.6–26.3), respectively; p = 0.01; odds ratio (OR) (95% confidence interval): 0.67 (0.49–0.90)); no such association was observed for men. In a multivariate analysis of the women, a lower leptin level was significantly associated with HAIs (OR = 0.70 (0.49–0.97)), independently of comorbidities, invasive medical procedures, and immune status. However, leptin was not significantly associated with HAIs after adjustments for malnutrition (p = 0.26) or albuminemia (p = 0.15)—suggesting that in older women, the association between serum leptin levels and subsequent HAIs is mediated by nutritional status

Citrulline prevents age-related LTP decline in old rats

International audienceThe prevalence of cognitive decline is increasing as the ageing population is considerably growing. Restricting this age-associated process has become a challenging public health issue. The age-related increase in oxidative stress plays a major role in cognitive decline, because of its harmful effect on functional plasticity of the brain, such as long-term potentiation (LTP). Here, we show that citrulline (Cit) has powerful antioxidant properties that can limit ex vivo oxidative stress-induced LTP impairment in the hippocampus. We also illustrate that a three-month Cit supplementation has a protective effect on LTP in aged rats in vivo. The identification of a Cit oxidation byproduct in vitro suggests that the antioxidant properties of Cit could result from its own oxidation. Cit supplementation may be a promising preventive nutritional approach to limit age-related cognitive decline

Proline Metabolism and Its Functions in Development and Stress Tolerance

Proline takes an exceptional place among the proteinogenic amino acids by its specific accumulation in pollen and in response to multiple types of stress. Despite the more than 50 years of research, the biochemical pathways of proline biosynthesis and degradation still await their complete characterization in plants. Also, the molecular and physiological functions of proline metabolism in plant development and defense against stress are not yet fully understood. This chapter focuses on the current knowledge about the biochemical pathways of proline metabolism in plants, on its tissue-specific regulation and subcellular compartmentation, and on still open questions. Furthermore, we will summarize what is known about the influence of proline metabolism on plant development under optimal growth conditions and how it may support continued development despite the impact of stress. The cognate chapter “Regulation of Proline Accumulation and its molecular and physiological Functions in Stress Defense” will focus on the possible beneficial functions of proline metabolism and accumulation in the defense response against diverse stresses. With these two cohesive chapters, we aim to provide a comprehensive picture of the current knowledge and the open research questions in proline-dependent stress defense