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    Amino Acid Metabolism and Immune Dysfunction in Urea Cycle Disorders: T and B Cell Perspectives
    (Wiley, 2025) Karaaslan, Betul Gemici; Kiykim, Ayca; Burtecene, Nihan; Gokden, Meltem; Cansever, Mehmet Serif; Hopurcuoglu, Duhan; Cengiz, Gokce Nuran
    Urea cycle disorders (UCDs) are a group of genetic metabolic conditions characterized by enzyme deficiencies responsible for detoxifying ammonia. Hyperammonemia, the accumulation of intermediate metabolites, and a deficiency of essential amino acids-due to a protein-restrictive diet and the use of ammonia scavengers-can increase the risk of infections, particularly during metabolic crises. While the underlying mechanisms of immune suppression are still being fully elucidated, hyperammonemia may impair the function of immune cells, particularly T cells and macrophages, inhibiting the proliferation of T cells and cytokine production. Arginine, which is essential for T-cell activation and function, may also be limited in these patients, and its depletion can increase their vulnerability to infections. Twenty-four UCD patients and 31 healthy donors were recruited for the study. Peripheral lymphocyte subset analysis, intracellular protein and cytokine staining, and proliferation assays were performed by flow cytometry. Amino acid levels were measured using the HPLC method. The UCD patients exhibited low lymphocyte-proliferation capacity in both proximal and distal defects in response to phytohaemagglutinin (PHA) and anti-CD2, anti-CD3, and anti-CD28 (CD-mix), which was lower than healthy controls. Proximal-UCD patients exhibited a significantly higher response for IFN-gamma compared to both distal-UCD patients and healthy controls. The different amino acids in the culture medium were changed significantly in the groups. This study highlights significant immune dysfunctions in UCD patients, particularly impaired T-cell proliferation and altered amino acid metabolism. Proximal UCD patients exhibited a higher IFN-gamma response, indicating a potential for hyperinflammation. Despite this, infection rates did not significantly differ between proximal UCD and distal UCD patients, although distal UCD patients had higher hospitalization rates. Amino acid analysis revealed distinct metabolic disruptions, emphasizing the complex interplay between metabolism and immune function. These findings suggest that UCDs cause profound immune alterations, necessitating further research to develop targeted therapeutic strategies.
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    Breath of relief: Transforming pediatric asthma care with telemedicine-guided exercises
    (Wiley, 2025) Karaaslan, Betul Gemici; Ucgun, Hikmet; Kaya, Meltem; Cengiz, Gokce Nuran; Ozturk, Sueda; Barut, Ozge; Korkut, Zeynep
    Background: Alternative non-pharmacological strategies such as breathing exercises can be used in combination with pharmacological treatments. Objective: The aim of this randomized, controlled, single-blind study was to investigate the effectiveness of breathing exercises in asthma patients on respiratory function, symptom control and quality of life. Methods: We enrolled pediatric asthma patients who were eligible and motivated for the study and randomly assigned them to either the exercise group (EG) or the control group (CG). The CG received a postural exercise program, while the EG received a breathing exercise program. At baseline and after 12 weeks, respiratory function (FEV1-FVC-FEV1/FVC-PEF), symptom control (using asthma control test, asthma control questionnaire, global initiative for asthma symptom control assessment), quality of life (using pediatric asthma quality of life questionnaire), breath-holding test (BHT) and sit-to-stand test (30sSTS) were assessed and compared. Results: One hundred twelve patients were randomized, and 99 (n = 51 EG, n = 48 CG) completed the 12-week study. Baseline data were also similar in both groups. After 12 weeks, FEV1, Peak expiratory flow (by spirometry and peak flow meter) and BHT were significantly better in EG than in CG (p = 0.01 and p = 0.007 and p = 0.005, respectively). Asthma Control Test and GINA symptom control tool values were also significantly better in both groups. Discussion:Our participants were children with mild to moderate asthma. We conclude that our results show that breathing exercises can be an effective intervention for children with partially controlled asthma with FEV1,PEF, and BHTs.