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Objectives: Reducing consumption of sugar-sweetened beverages (SSBs) is a primary public health goal in Thailand, but information on the characteristics of SSB consumers remains limited. This study aims to gain knowledge about the characteristics of SSB consumers in Thailand., Study Design: Secondary analysis of survey data., Methods: The study used data from the Health Behaviour of Population Survey conducted by Thailand's National Statistics Office between February and May 2021. SSB consumption was sourced from a survey question about the consumption of prepackaged sugar-sweetened non-alcoholic beverages. The influence of demographic, socioeconomic, behavioural, habitual, and health factors on mean daily intake and daily consumption was assessed using a two-part model and logistic regression analysis, respectively. Decomposition analysis was conducted to understand how the impact of these factors affecting SSB consumption varied across socioeconomic groups., Results: Frequent SSB consumers exhibited various unhealthy behaviours, including smoking, unhealthy food consumption, low physical activity, and making food selections driven by appetitive motivations. Although higher socioeconomic status was associated with greater consumption of SSBs, it stabilised at elevated income levels. Increased SSB consumption in higher socioeconomic groups was linked to mixed eating habits, being overweight, and occasional drinking, while in lower socioeconomic groups, it was associated with unhealthy behaviours like smoking, regular alcohol drinking, appetitive food choices, and low physical activity., Conclusions: SSB consumption in Thailand is multifactorial, varying by socioeconomic status. These insights are crucial for policy formation aimed at reducing SSB consumption in the country. Policymakers should explore interventions that address overall unhealthy behaviours alongside those targeting overconsumption of SSBs., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: The main objective was to use discrete event simulation to model the impact of wait-time, defined as the time between leukapheresis and chimeric antigen receptor (CAR-T) infusion, when assessing the cost-effectiveness of tisagenlecleucel in young patients with relapsed/refractory acute lymphoblastic leukemia., Methods: The movement of patients through the model was determined by parametric time-to-event distributions, with the competing risk of an event determining the costs and quality-adjusted life-years (QALYs) assigned. Cost-effectiveness was expressed using the incremental cost-effectiveness ratio (ICER) for tisagenlecleucel compared with chemotherapy over the lifetime., Results: The base case generated a total of 5.79 QALYs and $622 872 for tisagenlecleucel and 1.19 QALYs and $181 219 for blinatumomab, resulting in an ICER of $96 074 per QALY. An increase in mean CAR-T wait-time to 6.20 months reduced the benefit and costs of tisagenlecleucel to 2.78 QALYs and $294 478 because of fewer patients proceeding to infusion, reducing the ICER to $71 112 per QALY. Alternatively, when the cost of tisagenlecleucel was assigned pre-infusion in sensitivity analysis, the ICER increased with increasing wait-time., Conclusions: Under a payment arrangement where CAR-T cost is incurred post-infusion, the loss of benefit to patients is not reflected in the ICER. This may be misguiding to decision makers, where cost-effectiveness ratios are used to guide resource allocation. discrete event simulation is an important tool for economic modeling of CAR-T as it is amenable to capturing the impact of wait-time, facilitating better understanding of factors affecting service delivery and consequently informed decision making to deliver faster access to CAR-T for patients., Competing Interests: Author Disclosures Links to the disclosure forms provided by the authors are available here. The views expressed are those of the authors and not necessarily those of Novartis Pharmaceuticals or the Centre for Health Economics Research and Evaluation., (Copyright © 2024. Published by Elsevier Inc.)

Hydrogen peroxide (H2O2) present in honey was rapidly determined by the differential amperometric method in association with flow-injection analysis (FIA) and a tubular reactor containing immobilized enzymes. A gold electrode modified by electrochemical deposition of platinum was employed as working electrode. Hydrogen peroxide was quantified in 14 samples of Brazilian commercial honeys using amperometric differential measurements at +0.60V vs. Ag/AgCl((sat)). For the enzymatic consumption of H2O2, a tubular reactor containing immobilized peroxidase was constructed using an immobilization of enzymes on Amberlite IRA-743 resin. The linear dynamic range in H2O2 extends from 1 to 100 x 10(-6) mol L(-1), at pH 7.0. At flow rate of 2.0 mL min(-1) and injecting 150 microL sample volumes, the sampling frequency of the 90 determinations per hour is afforded. This method is based on three steps involving the flow-injection of: (1) the sample spiked with a standard solution, (2) the pure sample and (3) the enzymatically treated sample with peroxidase immobilized. The reproducibility of the current peaks for hydrogen peroxide in 10(-5) mol L(-1) range concentration showed a relative standard deviation (R.S.D.) better than 1%. The detection limit of this method is 2.9 x 10(-7) mol L(-1). The honey samples analyses were compared with the parallel spectrophotometric determination, and showed an excellent correlation between the methods.

Thiopurines are used for treatment of several diseases. Cytotoxicity is caused by the derived compounds 6-thioguanine nucleotides (TGNs) and methyl-6-thioinosine monophosphate (methylthio-IMP). The 6-thiopurine mononucleotides 6-thio-IMP (thio-IMP), 6-thio-GMP (thio-GMP) and methylthio-IMP can be catabolized by purine 5'-nucleotidase. It has been shown that the various 5'-nucleotidases are key enzymes for (6-thio)-purine metabolism. We aimed to investigate whether the overall 5'-nucleotidase (5'NT) activity is correlated with the efficacy and toxicity of 6-thiopurine nucleotides. Substrate affinity of 5'NT for IMP, GMP, AMP, thio-IMP, thio-GMP and methylthio-IMP was studied in human lymphocytes. For each of the substrates, the pH for optimal overall enzyme activity has been determined at a pH range between 6 and 10. At the optimal pH, assays were performed to establish Km and Vmax values. Optimal pH values for the various substrates were between 7 and 8.5. Km values ranged from 33 to 109 microM, Vmax ranged from 3.99 to 19.5 nmol/10(6) peripheral mononuclear cells (pMNC) h, and Vmax/Km ratios ranged from 105 to 250. The results did not show a distinct preference of 5'NT activity for any of the tested thiopurine nucleotides. The enzyme kinetic studies furthermore revealed substrate inhibition by thio-IMP and thio-GMP as a substrate. Inhibition by thio-GMP also seems to occur in patients treated with 6-mercaptopurine (6 MP); subsequently, this may lead to toxicity in these patients.

Thiopurine methyltransferase (TPMT) is an important enzyme in the metabolism of 6-mercaptopurine (6MP), which is used in the treatment of acute lymphoblastic leukemia (ALL). TPMT catalyzes the formation of methylthioinosine monophosphate (MetIMP), which is cytotoxic for cultured cell lines, and it plays a role in detoxification of 6MP. Population studies show a genetic polymorphism for TPMT with both high and low activity alleles. About 1 of 300 subjects is homozygous for the low activity. The function TPMT plays in detoxification or therapeutic efficacy of 6MP in vivo is not clear. In this article the genetic polymorphism of TPMT is reviewed and the contribution of TPMT to the cytotoxic action, or detoxification, of 6MP in children with ALL is discussed. Induction of TPMT activity has been described during the treatment for ALL. We performed a pilot study on the influence of high-dose 6MP infusions (1300 mg/m2 in 24 h) on TPMT activity of peripheral blood mononuclear cells (pMNC) of eleven patients with ALL. The TPMT activities were in, or, above the normal range. There was no statistically significant difference between the TPMT activities before and after the 6MP infusions. MetIMP levels in pMNC increased during successive courses. This might be explained by TPMT induction, but other explanations are plausible as well. Twenty five percent of the TPMT assays failed, because less than the necessary 5.10(6) pMNC could be isolated from the blood of leukopenic patients. Red blood cells can not be used for TPMT measurements, since transfusions are frequently required during the treatment with 6MP infusions. Therefore, the influence of high-dose 6MP infusions on TPMT activity can only be investigated further when a TPMT assay which requires less pMNC has been developed.

The thiopurine antimetabolites 6-thioguanine and 6-mercaptopurine are important chemotherapeutic drugs in the treatment of childhood acute lymphoblastic leukaemia. Measurement of metabolites of these thiopurines is important because correlations exist between levels of these metabolites and the prognosis in childhood acute lymphoblastic leukaemia. The reversed-phase method for the determination of extracellular thiopurine nucleosides and bases was previously developed and has been modified such that methylthiopurine nucleosides, bases, thioxanthine and thiouric acid can be measured also. The anion-exchange method enables the determination of intracellular mono-, di- and triphosphate (methyl)thiopurine nucleotides in one run. Extraction on ice with perchloric acid and dipotassium hydrogenphosphate results in good recoveries for (methyl)thiopurine nucleotides in lymphoblasts and peripheral mononuclear cells and for methylthioinosine nucleotides in red blood cells. Measurement of the low concentrations of mono-, di- and triphosphate thioguanine nucleotides in red blood cells (detection limit 20 pmol/10(9) cells) is possible after extraction with methanol and methylene chloride, followed by oxidation of thioguanine nucleotides with permanganate and fluorimetric detection.

Purine enzyme activities are usually assayed by radiochemical procedures and often TLC is part of the separation method. In screening patients with rheumatic diseases, these procedures have shown disadvantages like a relatively large coefficient of variation (C.V.) and time-instability. We describe a non-radiochemical reversed-phase HPLC micro-method with UV detection for measurement of activities of purine 5'-nucleotidase (5'NT; EC 3.1.3.5), purine nucleoside phosphorylase (PNP; EC 2.4.2.1) and hypoxanthine guanine phosphoribosyltransferase (HGPRT; EC 2.4.2.8) in human peripheral blood mononuclear cells (PBMC). The HPLC procedure is compared with the radiochemical TLC procedure by testing both with a 5'NT and a PNP assay. Reproducibility is tested with 14 healthy controls in each procedure. Short-term and long-term time-stability is tested by comparing enzyme activities measured immediately after preparation of the PBMC (week 0) with those found after freezing and storage at -20 degrees C for a maximum of 10 weeks. The HPLC procedure is preferable to the radiochemical TLC procedure because it shows significantly better reproducibility and better time-stability and in addition is non-radiochemical and less time-consuming.

In the urine of a child with unexplained convulsions large amounts of uracil and thymine were detected by gas chromatography. Identification was performed by coupled gas chromatography-mass spectrometry. Quantitation of the urinary excretion by means of a sensitive high-performance liquid chromatographic (HPLC) method revealed a 1000-fold elevation compared to normal. Serum and cerebrospinal fluid levels of the two pyrimidine bases were about a hundred times higher than normal. In fibroblasts the activity of dihydrothymine dehydrogenase was determined by measuring the conversion of radioactive labelled thymine to dihydrothymine with HPLC of the reaction mixture. In the patient's cells a complete deficiency of dihydrothymine dehydrogenase activity was found. Our patient is the first case described with such a proven enzyme deficiency.

A family with dihydropyrimidine dehydrogenase (DPD) deficiency is presented. In 3 persons a complete deficiency, and in 3 others a partial deficiency was detected in cultured fibroblasts. Two homozygote subjects and 1 heterozygote subject suffered from epileptic manifestations, in one of these homozygote subjects also microcephaly was found. DPD deficiency might be an etiological factor in the clinical picture of these patients. An autosomal recessive mode of inheritance of this deficiency was found.

One thousand specimens of CSF were collected from subjects ranging in age from newborn to 18 yr, who were undergoing a diagnostic lumbar puncture. Sixty-two samples were judged retrospectively as being suitable for calculating reference age-related values. The analyses were performed by an amino acid analyser using ion-exchange chromatography with fluorimetric detection giving a tenfold increase in sensitivity, thereby enhancing the diagnostic capabilities. As many as 36 known compounds could be detected, additionally 10 we could not identify. In children older than 3 yr nine of the identified compounds showed age-dependency. We found 22 amino acids to be significantly higher in infants younger than 1 yr, with only gamma-aminobutyric acid being significantly lower in infants. Alpha-aminoadipic acid showed a sex difference, being slightly higher in girls.

In three siblings with autosomal recessive idiopathic strio-pallido-dentate calcinosis (SPDC) and in three other siblings with Cockayne's syndrome (CS) studies on plasma values of calcium and phosphate, intestinal calcium absorption, radiograms of the hands and studies on the influence of parathyroid hormone (PTH) on the renal threshold for phosphate revealed no abnormalities. In one of the SPDC patients and one of the CS patients the effect of PTH on the cyclic adenosine monophosphate (cAMP) concentrations in urine and cerebrospinal fluid (CSF) were determined. In both a normal response of urinary cAMP was noted. In the CS patient the response of CSF cAMP was also normal. The SPDC patient, however, had a significantly decreased response of CSF cAMP. It is suggested that a decreased sensitivity of the cerebral adenylate cyclase complex is involved in the etiology of autosomal recessive idiopathic SPDC. Subsequently this disorder could be considered as cerebral pseudohypoparathyroidism. The etiology of CS remains unknown.

A method for the identification and quantitation of nucleotide pools in lymphocytes and leukemic blasts is described. Separation of these metabolites was performed by anion-exchange high-performance liquid chromatography using a pH and concentration gradient consisting of several linear steps. The mono-, di- and triphosphates of adenosine, cytidine, guanosine, inosine, uridine and xanthosine could conveniently be separated together with NAD+, cyclic AMP, NADP+ and uridinediphosphoglucose (UDPG). In addition, data on the accuracy and precision of the method are given and its potentials for use in the analysis of nucleotide pools in leukemic lymphoblasts are illustrated.

A method is presented for the separation and quantitative determination of compounds normally related to purine and pyrimidine metabolism in biological material. The retention behaviour of nucleobases, ribonucleosides, deoxyribonucleosides and cyclic ribonucleotides has been systematically investigated by reversed-phase high-performance liquid chromatography using a non-linear gradient. Ultimately a separation of the purine and pyrimidine compounds was achieved in a 35-min run with an average detection limit of 5-10 pmol per injection. Recoveries of standards added to urine, plasma or serum were 96 +/- 5%.