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Background: High-dose methotrexate (HD-MTX) is seen as an effective therapy for acute lymphoblastic leukemia (ALL); however, it is extremely toxic. Monitoring the plasma concentrations of methotrexate (MTX) and its important metabolite, 7-hydroxy-methotrexate (7-OH-MTX), on a routine basis aids in dose modification of rescue medications and in avoiding toxicity. The pharmacologically active and toxic effects of drugs are due to the unbound portion, as most drugs are bound to plasma proteins to some degree. However, the simultaneous measurement of unbound plasma concentrations of MTX and 7-OH-MTX has not been reported.
Methods: We developed and validated a hollow fiber centrifugal ultrafiltration (HFCF-UF) technology to simultaneously analyze unbound MTX and 7-OH-MTX concentrations in human plasma. In total, 234 plasma samples from 58 children diagnosed with ALL who were administered HD-MTX were used in our study. We investigated the connection between unbound and total plasma concentrations of MTX and 7-OH-MTX, as well as how these concentrations relate to liver and renal function.
Results: The method that was developed is both simple and accurate. A weak linear relationship was observed between the concentrations of unbound and total 7-OH-MTX ( = 0.732). The concentration of total MTX and unbound 7-OH-MTX were both positively correlated with creatinine (Cr) levels and negatively correlated with Creatinine clearance (CCr). There was a wide variation in the concentration ratios of 7-OH-MTX to MTX, both total and unbound, and these ratios were significantly lower in individuals with impaired liver function.
Conclusion: The total concentration of 7-OH-MTX is an unreliable predictor of unbound concentration, necessitating the monitoring of unbound levels. The concentration ratios of 7-OH-MTX to MTX (both total and unbound) could be more accurate and sensitive biomarkers for predicting hepatotoxicity.
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http://dx.doi.org/10.2147/DDDT.S516431 | DOI Listing |
Anal Chim Acta
November 2025
Institute of Nano Science and Technology, Knowledge City, Sahibzada Ajit Singh Nagar, Sector- 81, Punjab, 140306, India. Electronic address:
Background: Iron (Fe) is an essential micronutrient for plant growth, but the conventional DTPA soil analysis method for detecting available iron has notable limitations, requiring advanced instruments and lengthy preparation time. Developing a more affordable, user-friendly, and efficient method for iron detection in soil could greatly improve crop nutrition management. Here, a facile nanoscopic method was developed to quantify available Fe ions in the soil by forming a luminescence quenching complex in chelation with bathophenanthroline disulphonic acid disodium salt (Fe/BPDS complex).
View Article and Find Full Text PDFClin Chim Acta
September 2025
Department of Clinical Laboratory, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China. Electronic address:
Infection with SARS-CoV-2 elevates the expression of cytokines, resulting in a cytokine storm that serves as the primary factor for severe illness and mortality; however, effective markers for predicting disease severity and preventing are lacking. Thus, we investigated the association between serum levels of nerve injury-induced protein 1 (Ninj1), a mediator of plasma membrane rupture, and the extent of lung damage in COVID-19 patients was examined to anticipate the severity of SARS-CoV-2 infection. This study included 62 healthy participants and 264 patients with COVID-19.
View Article and Find Full Text PDFInt J Antimicrob Agents
September 2025
Department of Clinical Pharmacy and Pharmacy Administration, School of Pharmacy, Fudan University, Shanghai, China; National Key Laboratory of Advanced Drug Formulations for Overcoming Delivery Barriers, Fudan University, Shanghai, China. Electronic address:
Background: This study characterized the urinary pharmacokinetics and pharmacodynamics (PK/PD) of linezolid (LNZ) in critically ill patients with renal impairment and nosocomial multidrug-resistant Gram-positive urinary tract infections (UTIs). The aim was to address therapeutic challenges arising from limited treatment options and uncertain urinary excretion, to establish optimized dosing strategies.
Methods: A prospective observational study was conducted in ICU patients with renal impairment.
Food Chem
August 2025
College of Environmental and Resource Sciences, Zhejiang University, Hangzhou 310058, China; State Key Laboratory of Soil Pollution Control and Safety, Zhejiang University, Hangzhou 310058, China; Innovation Center of Yangtze River Delta, Zhejiang University, Jiaxing 314102, China. Electronic addres
This study investigated the spatial distribution of Cd and mineral nutrients (Mg, P, K, Ca, Mn, Fe, Cu, Zn) in rice grains from low-Cd accumulating (LA) and high-Cd accumulating (HA) cultivars using laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS). Cd concentrations were significantly higher in HA than LA cultivars across polished rice, brown rice, and husks. Spatial mapping demonstrated Cd was distributed in the outer endosperm/embryo of LA grains, but preferentially enriched in the embryo and aleurone layer of HA grains.
View Article and Find Full Text PDFPoult Sci
August 2025
Central Queensland Innovation and Research Precinct (CQIRP), Institute for Future Farming Systems, Central Queensland University, Rockhampton, QLD 4701, Australia; Department of Physiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
This study evaluated the efficacy of Eucalyptus globulus essential oil (EEO) supplementation in attenuating ascites incidence and physiological disturbances in broiler chickens exposed to a cold-induced pulmonary hypertension syndrome model. A total of 720 one-day-old male Ross 308 chicks were randomly assigned to six dietary treatments, each with six replicates of 20 birds. The thermoneutral control group received a basal diet under standard conditions (32°C on day 1, gradually reduced to 23°C by day 20 and maintained until day 42; relative humidity [RH] 50-60 %), whereas the remaining five groups were exposed to cold stress (temperature reduced by 4°C/day from day 11 until reaching 15°C, then maintained at 10-15°C until day 42, RH 55-65 %) to induce ascites, and were fed the basal diet supplemented with 0, 500, 1000, 1500, or 2000 mg/kg EEO.
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