This tutorial explains the pharmacokinetics of a prodrug and its active metabolite (or parent drug) using a two-step, consecutive, first-order irreversible reaction as a basic model for prodrug metabolism. In this model, the prodrug is metabolized and produces the parent drug, which is subsequently eliminated. The mathematical expressions for pharmacokinetic parameters were derived step by step. In addition, we visualized these expressions to help understand the relationship between pharmacokinetic parameters easily. For the elimination rate-limited and formation rate-limited metabolism, we analyzed the plasma drug concentration versus time curve of a prodrug administered intravenously.
Humans ; Metabolism ; Parents ; Pharmacokinetics ; Plasma

Humans ; Liver Diseases ; blood ; Plasma ; metabolism ; Proteome

INTRODUCTION: Acylcarnitines in plasma and urinary organic acids are essential diagnostic markers for some Inborn Errors of Metabolism (IEM) such as fatty acid oxidation disorders, and disorders related to organic acids metabolism. By virtue of R. A. 9288, Filipino newborn babies are screened for inherited metabolic disorders via the analysis of dried blood spots (DBS) using MS/MS. OBJECTIVE: This study aimed to establish the plasma acylcarnitine (PLAC) and urinary organic acid (UOA) profiles of Filipino newborn babies screened at high risk for IEMS using MS/MS and single quadrupole GC-MS analytical techniques. Further, this study describes the process of determining the true positive cases of fatty acid oxidation disorders and some organic acidurias among screened Filipino newborn babies using different sample types such as plasma and urine via flow injection analysis with tandem mass spectrometry (FIA-MS/MS) and another technique such as gas chromatography in tandem with mass spectrometry (GC-MS). METHODOLOGY: Plasma acylcarnitine and urinary organic acid analyses were performed using Waters® MS/MS and Agilent® single quadrupole GC-MS, respectively. Results obtained from PLAC and UOA databases and IEM registry of the Biochemical Genetics Laboratory (BGL) covering the period 2015-2021 were utilized to account for the number of confirmed cases out of the total number screened positive for IEMs. Descriptive statistics was also used to evaluate the detection rates of FAODs and Organic Acidurias in Filipino newborn babies screened to be high risk. RESULTS: Plasma acylcarnitine analysis was introduced by BGL only in 2015. Data from 2015-2021, indicated 176 true positives out of 1642 babies screened at high risk for FAODs and organic acidurias. The use of plasma and urine samples for measurements in MS/MS and GC-MS yielded a detection rate of 10.7% with 104 Filipino newborn babies afflicted with fatty acid oxidation disorders (FAOD) while 72 were found to be confirmed cases of organic acidurias. Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency was reported to be the most common FAOD with 67 cases. Organic acidurias such as glutaric aciduria type 1 and 3-Methylcrotonyl-CoA carboxylase (3-MCC) deficiency were found to be common with 34 and 26 true positives, respectively. CONCLUSION The plasma acylcarnitine and urinary organic acid profiles of Filipino newborn babies with fatty acid oxidation disorders and organic acidurias obtained via MS/MS and GC/MS, respectively, were presented in this paper. This study emphasizes the importance of conducting confirmatory testing to establish the true positives from among those Filipino newborns flagged to be at high risk for FAODs or organic aciduria. The confirmatory tests are based on the use of different samples such as urine and plasma in order to detect and quantify biomarkers for FAODs and organic acidurias using two different analytical techniques such as MS/MS and GC-MS. This study warrants further studies directed towards the validation of analytical methodologies for targeted measurements of biomarkers of IEMS in urine and plasma of newborn babies to increase the efficiency of establishing true positives and to determine the efficiency of administration of interventions on Filipino children with genetic disabilities, that is, for monitoring purposes.
plasma ; inborn error of metabolism ; tandem mass spectrometry ; GC-MS

Adsorption ; Bilirubin ; metabolism ; Liver, Artificial ; Plasma Exchange ; methods

Rapidly proliferating cancer cells require energy and cellular building blocks for their growth and ability to maintain redox balance. Many studies have focused on understanding how cancer cells adapt their nutrient metabolism to meet the high demand of anabolism required for proliferation and maintaining redox balance. Glutamine, the most abundant amino acid in plasma, is a well-known nutrient used by cancer cells to increase proliferation as well as survival under metabolic stress conditions. In this review, we provide an overview of the role of glutamine metabolism in cancer cell survival and growth and highlight the mechanisms by which glutamine metabolism affects cancer cell signaling. Furthermore, we summarize the potential therapeutic approaches of targeting glutamine metabolism for the treatment of numerous types of cancer.
Cell Survival ; Glutamine ; Metabolism ; Oxidation-Reduction ; Plasma ; Stress, Physiological

OBJECTIVES: To explore the correlation between cytosine-phosphoric-guanylic (CpG) site of Septin 9 gene and colorectal cancer, and to develop a real-time PCR detection system in plasma in patients with colorectal cancer. METHODS: The methylation of training samples was detected by high-throughput sequencing technology, and the sites highly consistent with the clinical information of colorectal cancer were identified. Then the detection system of real-time PCR was designed to analyze the consistency of plasma and tissue based on methylationa sensitive enzyme digestion. Finally, 100 clinical trials were conducted to evaluate the performance of the detection system with the methylation sensitive enzyme digestion-real-time PCR. RESULTS: The highly consistent sites, which were selected by high-throughput sequencing from 71 training set samples, was the 38th CpG. Based on the detection region, the screened methylation sensitive enzymes were CONCLUSIONS The 38th CpG site of Septin 9 detected by the detection system of methylation sensitive enzyme digestion-real-time PCR can highly predict the occurrence of colorectal cancer with great clinical application value.
Colorectal Neoplasms/genetics* ; CpG Islands/genetics* ; DNA ; DNA Methylation ; Humans ; Plasma/metabolism* ; Septins/metabolism*

Platelet-enriched plasma (PRP) contains high concentration of platelets and abundant growth factors, which is made by centrifuging of blood and separating of blood elements. PRP promotes tendon repair by releasing various cytokines to enhance cell proliferation, tenogenic differentiation, formation and secretion of matrix; meantime, it can reduce pain by inhibiting the expression of pain-associated molecules. A number of clinical studies demonstrated that PRP was effective in treatment of tendinopathy, including patellar tendinopathy, lateral epicondylitis and plantar fasciopathy. However, some studies did not support this conclusion, because of disparity of PRP types, therapeutic courses and injections protocols in clinical application. Based on its safety, PRP can be a choice of treatment for tendinopathy, in case other non-surgical therapies are of no effect.
Blood Platelets ; cytology ; Cytokines ; metabolism ; Humans ; Intercellular Signaling Peptides and Proteins ; metabolism ; Platelet-Rich Plasma ; Tendinopathy ; therapy

Cartilage, Articular ; metabolism ; Humans ; Osteoarthritis, Knee ; blood ; Platelet-Rich Plasma ; metabolism

The purpose of the present study was to investigate the effects of cornel iridoid glycoside (CIG) on the activity of cholinesterases in vitro, and to investigate the mechanism of CIG's treating Alzheimer's disease (AD). The sources of cholinesterases were prepared from human blood cells, rat brain homogenate and human blood plasma, respectively. The biochemical methods were used to detect the activity of acetylcholine esterase (AChE) and butyryl cholinesterase (BuChE) to investigate the influence of CIG on cholinesterases. The results showed that CIG inhibited the activity of AChE of human blood cells and rat brain homogenate, with the 50% inhibition rate (IC50) of 1.6 g . L-1 and 3.3 g . L-1, respectively; and the inhibition of AChE of CIG is reversible. CIG also inhibited the activity of BuChE of human blood plasma, with the IC50 of 2.9 g . L-1. In conclusion, CIG can inhibit the activity of AChE and BuChE in vitro, which may be one of the mechanisms of CIG to treat AD.
Acetylcholinesterase ; metabolism ; Animals ; Brain ; drug effects ; metabolism ; Cholinesterase Inhibitors ; pharmacology ; Cholinesterases ; metabolism ; Humans ; Iridoid Glycosides ; pharmacology ; Plasma ; enzymology ; Rats

Escherichia coli AFP111 is a spontaneous mutant with mutations in the glucose specific phosphotransferase system (ptsG) in NZN111 (delta pflAB deltaldhA). In AFP111, conversion of xylose to succinic acid generates 1.67 molecule of ATP per xylose. However, the strain needs 2.67 molecule ATP for xylose metabolism. Therefore, AFP111 cannot use xylose due to insufficient ATP under anaerobic condition. Through an atmospheric and room temperature plasma (ARTP) jet, we got a mutant strain named DC111 that could use xylose under anaerobic condition in M9 medium to produce succinic acid. After 72 h, DC111 consumed 10.52 g/L xylose to produce 6.46 g/L succinic acid, and the yield was 0.78 mol/mol. Furthermore, the reaction catalyzed by the ATP-generating PEP-carboxykinase (PCK) was enhanced. The specific activity of PCK was 19.33-fold higher in DC111 than that in AFP111, which made the strain have enough ATP to converse xylose to succinic acid.
Atmosphere ; Escherichia coli ; genetics ; metabolism ; Fermentation ; Industrial Microbiology ; Metabolic Engineering ; Mutation ; Plasma Gases ; pharmacology ; Succinic Acid ; metabolism ; Temperature ; Xylose ; metabolism