POBS-Card, a new score of severe bleeding after cardiac surgery: Construction and external validation.

Objective: Bleeding after cardiac surgery leads to poor outcomes. The objective of the study was to build the PeriOperative Bleeding Score in Cardiac surgery (POBS-Card) to predict bleeding after cardiac surgery.

Methods: We conducted a retrospective cohort study in 2 academic hospitals (2016-2019).

Effect of short- and long-term treatment with valproate on carnitine homeostasis in humans.

Aims: The aim of this study was to identify the mechanisms of hypocarnitinemia in patients treated with valproate.

Methods: Plasma concentrations and urinary excretion of carnitine, acetylcarnitine, propionylcarnitine, valproylcarnitine, and butyrobetaine were determined in a patient starting valproate treatment and in 10 patients on long-term valproate treatment. Transport of carnitine and valproylcarnitine by the proximal tubular carnitine transporter OCTN2 was assessed in vitro.

The plasma carnitine concentration regulates renal OCTN2 expression and carnitine transport in rats.

Previous findings in rats and in human vegetarians suggest that the plasma carnitine concentration and/or carnitine ingestion may influence the renal reabsorption of carnitine. We tested this hypothesis in rats with secondary carnitine deficiency following treatment with N-trimethyl-hydrazine-3-propionate (THP) for 2 weeks and rats treated with excess L-carnitine for 2 weeks. Compared to untreated control rats, treatment with THP was associated with an approximately 70% decrease in plasma carnitine and with a 74% decrease in the skeletal muscle carnitine content.

Urinary excretion of carnitine as a marker of proximal tubular damage associated with platin-based antineoplastic drugs.

Background: Patients treated with cisplatin or carboplatin show increased renal excretion of carnitine. It is currently unclear whether this is also the case for oxaliplatin and which are the responsible mechanisms.

Methods: We investigated 22 patients treated either with a single dose of cisplatin, carboplatin or oxaliplatin.

Interaction between pivaloylcarnitine and L-carnitine transport into L6 cells overexpressing hOCTN2.

Patients ingesting pivalic acid containing prodrugs develop hypocarnitinemia. Pivalic acid is cleaved from such drugs and excreted renally as pivaloylcarnitine. Plasma concentrations (reflecting the concentration in the glomerular filtrate entering the proximal tubule) in patients treated with cefditoren pivoxil are approximately 5 microM for pivaloylcarnitine and 10 microM for carnitine.

Effect of carnitine deprivation on carnitine homeostasis and energy metabolism in mice with systemic carnitine deficiency.

Background/aims: Juvenile visceral steatosis (jvs-/-) mice lack the activity of the carnitine transporter OCTN2 and are dependent on carnitine substitution. The effects of carnitine deprivation on carnitine homeostasis and energy metabolism are not known in jvs-/- mice.

Methods: jvs-/- mice were studied 3, 6 and 10 days after carnitine deprivation, and compared to jvs-/- mice substituted with carnitine, wild-type (jvs+/+) and jvs+/- mice.

Pharmacological manipulation of L-carnitine transport into L6 cells with stable overexpression of human OCTN2.

The high-affinity Na+-dependent carnitine transporter OCTN2 (SLC22A5) has a high renal expression and reabsorbs most filtered carnitine. To gain more insight into substrate specificity of OCTN2, we overexpressed hOCTN2 in L6 cells and characterized the structural requirements of substances acting as human OCTN2 (hOCTN2) inhibitors. A 1905-bp fragment containing the hOCTN2 complete coding sequence was introduced into the pWpiresGFP vector, and L6 cells were stably transduced using a lentiviral system.

Toxicity of valproic acid in mice with decreased plasma and tissue carnitine stores.

The aim of this study was to investigate whether a decrease in carnitine body stores is a risk factor for valproic acid (VPA)-associated hepatotoxicity and to explore the effects of VPA on carnitine homeostasis in mice with decreased carnitine body stores. Therefore, heterozygous juvenile visceral steatosis (jvs)(+/-) mice, an animal model with decreased carnitine stores caused by impaired renal reabsorption of carnitine, and the corresponding wild-type mice were treated with subtoxic oral doses of VPA (0.1 g/g b.

Effect of St John's wort on the activities of CYP1A2, CYP3A4, CYP2D6, N-acetyltransferase 2, and xanthine oxidase in healthy males and females.

Aims: To investigate the influence of St. John's wort (SJW) on CYP3A4, CYP1A2, CYP2D6, N-acetyltransferase 2 (NAT2), and xanthine oxidase (XO) activities in healthy males and females.

Methods: Eight males and eight females were treated with SJW extract (3 x 300 mg day(-1)) for 14 days.

Determination of -3858G-->A and -164C-->A genetic polymorphisms of CYP1A2 in blood and saliva by rapid allelic discrimination: large difference in the prevalence of the -3858G-->A mutation between Caucasians and Asians.

Introduction: Two mutations in CYP1A2, -164C-->A (allele CYP1A2*F) and -3858G-->A (allele CYP1A2*C), affecting the inducibility of the enzyme, have been published. The aim of this study was to develop a high throughput allelic discrimination assay for these mutations in both saliva and blood and to determine their frequency in Caucasians.

Methods: An allelic discrimination assay, based on the fluorogenic 5'-nuclease activity (TaqMan), was developed for the two mutations.

Effect of low doses of 5-methyltetrahydrofolate and folic acid on plasma homocysteine in healthy subjects with or without the 677C-->T polymorphism of methylenetetrahydrofolate reductase.

Background: The 677C-->T polymorphism of methylenetetrahydrofolate reductase can lead to increased homocysteine. Moderate increases of homocysteine can be lowered by folic acid (0.4-10 mg day-1).

Regulation of connective tissue growth factor gene expression in retinal vascular endothelial cells by angiogenic growth factors.

Background: Connective tissue growth factor (CTGF) is a novel, cysteine-rich secreted protein, which is implicated in fibrotic disorders and atherosclerosis. To elucidate the role of CTGF in fibrovascular proliferative retinopathy, we investigated the regulation of CTGF gene expression in a cell line of retinal vascular endothelial cells (RVEC) stimulated with fetal calf serum (FCS) and angiogenic growth factors, including vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), platelet-derived growth factor-BB (PDGF-BB), endothelial growth factor (EGF), transforming growth factor-beta 1 and -beta 3 (TGF-beta 1, TGF-beta 3), and insulin-like growth factor-I (IGF-I).

Methods: RVEC derived from Macaca mulatta (CRL-1780; ATCC) were stimulated with 10% FCS as well as with VEGF, bFGF, PDGF-BB, TGF-beta 1, TGF-beta 3, EGF, or IGF-I.

Methylenetetrahydrofolate reductase polymorphism, plasma homocysteine and age.

Background: Elevated fasting levels of total homocysteine are now accepted as an independent risk factor for the development of arteriosclerotic vascular diseases. A polymorphism in the gene encoding methylenetetrahydrofolate reductase (MTHFR), caused by the C677T point mutation, leads to increased thermolability of the enzyme, with reduced enzyme activity. We studied the frequency of this mutation in different groups of the Swiss adult population.

Acetaminophen is an inhibitor of hepatic N-acetyltransferase 2 in vitro and in vivo.

Slow acetylators of the polymorphic N-acetyltransferase 2 (NAT2, EC 2.3.1.

Quantitative determination of tolazoline in human serum by high performance liquid chromatography.

A micro high performance liquid chromatography assay is reported for the measurement of tolazoline in newborn infants. Pharmacokinetic data are presented for a single infant receiving tolazoline therapy. Tolazoline and the internal standard, clonidine, are extracted from alkaline serum into butylchloride/isopropanol (95/5).