Background And Objectives: The recombinant human growth hormone (rhGH) is being increasingly used for a number of metabolic alterations. GH is the main regulator of several hepatic drug metabolizing enzymes in rodents. In addition, GH could play a major role in defining the interface between pharmacogenetics and development. However, little is known about the effect of GH on the activity of hepatic enzymes in children. The aim of this study was to determine the effect of rhGH replacement therapy for 4 weeks on CYP1A2 and xanthine oxidase (XO) activities in children.
Methods: We used caffeine as a probe drug to assess the enzyme activities at two points in time: before starting GH treatment (day 0) and after 4 weeks on rhGH therapy (day A). A total of 31 GH-deficient children (age range: 4.1-13.1 years, mean age: 9.88+/-2.89 years) participated. Urinary concentrations of caffeine and metabolites were determined by high-performance liquid chromatography (HPLC) to calculate the metabolite ratios: (AFMU+1X+1U)/17U for CYP1A2 and 1U/(1X+1U) for XO.
Results: Four weeks of GH substitution did not importantly alter the markers of the enzyme activities measured in this study. Median values and 95% confidence intervals (CI) at baseline were 5.17 (3.87-5.59) for the CYP1A2 ratio and 0.62 (0.56-0.65) for the XO ratio. These values, after treatment, were 4.57 (3.90-5.97) for the CYP1A2 marker and 0.62 (0.59-0.67) for the XO ratio. Data comparison between periods showed lack of statistically significant differences (P>0.05). The relative changes measured by the ratios of medians and 90% CI were 1.14 (0.90-1.31) and 0.99 (0.94-1.06) for CYP1A2 and XO, respectively.
Conclusions: The absence of significant changes in the markers of enzyme activities CYP1A2 and XO suggests that rhGH replacement therapy of GH-deficient children for 4 weeks could not noticeably modify the efficacy or toxicity of substrates of these metabolic enzymes.
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http://dx.doi.org/10.1007/s00228-005-0082-y | DOI Listing |
Front Physiol
December 2024
Department of Nephrology, Tangdu Hospital, The Fourth Military Medical University, Air Force Medical University, Xi'an, Shaanxi Province, China.
Background: Plasma oxidized lipids are intimately linked to immune regulation as bioactive mediators. However, it is not clear whether they are related to the progression of sepsis-associated acute kidney injury (SA-AKI) and the effect of continuous renal replacement therapy (CRRT). This study intends to explore the changes in certain oxidized lipid during CRRT treatment and their correlation with the immune microenvironment and prognosis by analyzing plasma oxidative lipidomics.
View Article and Find Full Text PDFMol Ther Methods Clin Dev
December 2024
Research Institute, Children's Hospital of Orange County, Orange, CA, USA.
Mucopolysaccharidosis type I (MPS I) is a metabolic disorder characterized by a deficiency in α-l-iduronidase (IDUA), leading to impaired glycosaminoglycan degradation. Current approved treatments seek to restore IDUA levels via enzyme replacement therapy (ERT) and/or hematopoietic stem cell transplantation (HSCT). The effectiveness of these treatment strategies in preventing neurodegeneration is limited due to the inability of ERT to penetrate the blood-brain barrier (BBB) and HSCT's limited CNS reconstitution of IDUA levels.
View Article and Find Full Text PDFFront Endocrinol (Lausanne)
December 2024
Department of Cardiovascular Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
Introduction: The Sequential Organ Failure Assessment (SOFA) score is a widely utilized clinical tool for evaluating the severity of organ failure in critically ill patients and assessing their condition and prognosis in the intensive care unit (ICU). Research has demonstrated that higher SOFA scores are associated with poorer outcomes in these patients. However, the predictive value of the SOFA score for acute kidney injury (AKI), a common complication of diabetic ketoacidosis (DKA), remains uncertain.
View Article and Find Full Text PDFFront Oncol
December 2024
Department of Neurosurgery, West China Hospital/West China School of Medicine, Sichuan University, Chengdu, Sichuan, China.
Craniopharyngioma is a rare, benign tumor that originates from the pituitary stalk and extends along the pituitary-hypothalamic axis. It can have serious effects due to its location, affecting hormone regulation, vision, and other neurological functions. It is particularly rare and challenging to manage it during pregnancy due to the potential impacts on both maternal and fetal health, requiring careful, individualized treatment.
View Article and Find Full Text PDFRen Fail
December 2025
Department of Nephrology, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen, Guangdong Province, China.
Background: Acute kidney injury (AKI) is a common complication in critically ill patients, with approximately 5% requiring continuous renal replacement therapy (CRRT). This study investigated the relationship between mean arterial pressure (MAP) and 28- and 90-day mortality in critically ill AKI patients treated with CRRT.
Methods: This secondary analysis of a bicenter, retrospective, observational study included patients with AKI who were treated with CRRT from January 2009 to September 2016.
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