Search results for "metabolite"
showing 10 items of 551 documents
Determination of haemoglobin adducts of acrylamide and glycidamide in smoking and non-smoking persons of the general population
2005
Acrylamide (AA) is a food-borne toxicant suspected to be carcinogenic to humans. It is formed in the heating process of starch-containing food. Currently, there is a great discussion about the possible human health risks connected with the dietary uptake of acrylamide. Haemoglobin adducts of acrylamide and its oxidative metabolite glycidamide are both markers of biochemical effect. However, because glycidamide has a higher carcinogenic potency than acrylamide itself, the glycidamide adduct might mirror the genotoxicity better than acrylamide adducts. In order to gain more information about the human metabolism of acrylamide, we investigated a small group of persons for the effective interna…
Glycerophosphocholine is elevated in cerebrospinal fluid of Alzheimer patients.
2003
Experimental and clinical studies give evidence for breakdown of membrane phospholipids during neurodegeneration. In the present study, we measured the levels of glycerophosphocholine (GPCh), phosphocholine (PCh), and choline, that is, water-soluble metabolites of phosphatidylcholine (PtdCho), in human cerebrospinal fluid (CSF). Among 30 cognitively normal patients the average CSF levels of GPCh, phosphocholine and choline were 3.64, 1.28, and 1.93 microM, respectively; metabolite levels did not change with increasing age. When compared with age-matched controls, patients with Alzheimer's disease had elevated levels of all choline metabolites: GPCh was significantly increased by 76% (P<0.01…
Adjuvant vs. neoadjuvant radiochemotherapy for locally advanced rectal cancer: the German trial CAO/ARO/AIO-94.
2003
Aim The standard treatment for patients with clinically resectable rectal cancer is surgery. Postoperative radiochemotherapy (RCT) is recommended for advanced disease (pT3/4 or pN+). In recent years, encouraging results of pre-operative radiotherapy have been reported. This prospective randomized phase-III-trial (CAO/ARO/AIO-94) compares the efficacy of neoadjuvant RCT to standard postoperative RCT. We report on the design of the study and first results with regard to toxicity of RCT and postoperative morbidity. Patients and methods Patients with locally advanced operable rectal cancer (uT3/4 or uN+, Mason CS III/IV) were randomly assigned to pre or postoperative RCT: A total dose of 50.4…
Allogeneic Hematopoietic Stem Cell Transplantation Following the Use of Hypomethylating Agents among Patients with Relapsed or Refractory AML: Findin…
2018
Patients with primary refractory or relapsed acute myeloid leukemia (RR-AML) have very poor prognosis. Due to limited treatment options, some patients are treated with hypomethylating agents (HMAs) due to their tolerability. Little is known about the role of allogeneic hematopoietic stem cell transplantation (HSCT) following HMA therapy in this setting. We retrospectively analyzed an international cohort of 655 RR-AML patients who received HMA therapy to study patterns and outcomes with HSCT. Only 37 patients (5.6%) patients underwent HSCT after HMA therapy. The conditioning regimen was myeloablative in 57% and nonmyeloablative in 43%. Patients received matched unrelated donor, matched sibl…
CYP2D6 polymorphism and clinical effect of the antidepressant venlafaxine.
2006
SUMMARY Background: Venlafaxine (V) is a mixed serotoninand noradrenaline reuptake inhibitor used as afirst-line treatment of depressive disorders. It ismetabolized primarily by the highly polymorphiccytochrome P450 (CYP) enzyme CYP2D6 to yielda pharmacologically active metabolite, O-des-methylvenlafaxine (ODV), and to a lesser extentby CYP3A4, to yield N-desmethylvenlafaxine(NDV).Objectives: The aim of this study was to assesswhether the O-demethylation phenotype of V hasan impact on the pharmacokinetics and clinicaloutcome.Method: In 100 patients treated with V, serumconcentrations of V, ODV and NDV and theratios of concentrations ODV/V as a measure ofO-demethylation were determined. Indiv…
Cetuximab with irinotecan, folinic acid and 5-fluorouracil as first-line treatment in advanced gastroesophageal cancer: a prospective multi-center bi…
2011
Abstract Background Cetuximab plus irinotecan/folinic acid/5-fluorouracil (5-FU) (IF) was evaluated as first-line treatment of patients with advanced gastric cancer and gastroesophageal junction tumors. Preplanned analyses of the influence of tumor biomarkers on treatment outcome were carried out. Patients and methods Patients received weekly cetuximab (400 mg/m2 on day 1, subsequently 250 mg/m2) plus irinotecan (80 mg/m2) and a 24-hour continuous infusion of folinic acid (200 mg/m2) and 5-FU (1500 mg/m2) on days 1, 8, 15, 22, 29 and 36 of a 50-day cycle, until progressive disease (PD). Results The most common grade 3/4 toxic effects in 49 patients were diarrhea (15%) and skin toxic effects…
Medium chain acylcarnitines dominate the metabolite pattern in humans under moderate intensity exercise and support lipid oxidation.
2010
BACKGROUND: Exercise is an extreme physiological challenge for skeletal muscle energy metabolism and has notable health benefits. We aimed to identify and characterize metabolites, which are components of the regulatory network mediating the beneficial metabolic adaptation to exercise. METHODOLOGY AND PRINCIPAL FINDINGS: First, we investigated plasma from healthy human subjects who completed two independent running studies under moderate, predominantly aerobic conditions. Samples obtained prior to and immediately after running and then 3 and 24 h into the recovery phase were analyzed by a non-targeted (NT-) metabolomics approach applying liquid chromatography-qTOF-mass spectrometry. Under t…
Therapeutic Drug Monitoring of the Antidepressant Mirtazapine and Its N-Demethylated Metabolite in Human Serum
2004
Mirtazapine is a novel antidepressant that acts by enhancing serotonergic and noradrenergic neurotransmission. Because very little is known about serum concentrations in relation to clinical effects, the use of therapeutic drug monitoring is so far unclear. A rapid automated HPLC method with fluorescence detection was developed for routine quantification of mirtazapine and its demethylated metabolite N-desmethylmirtazapine in human serum. The precision of the method was suitable because the day-to-day (n = 7) coefficient of variation (CV) of mirtazapine was 9.8, 4.2, and 5.1% for concentrations of 10, 40, and 80 ng/mL, respectively, and the CV for N-desmethylmirtazapine were 11.6, 10.3, and…
Ex vivo high resolution magic angle spinning metabolic profiles describe intratumoral histopathological tissue properties in adult human gliomas.
2010
In gliomas one can observe distinct histopathological tissue properties, such as viable tumor cells, necrotic tissue or regions where the tumor infiltrates normal brain. A first screening between the different intratumoral histopathological tissue properties would greatly assist in correctly diagnosing and prognosing gliomas. The potential of ex vivo high resolution magic angle spinning spectroscopy in characterizing these properties is analyzed and the biochemical differences between necrosis, high cellularity and border tumor regions in adult human gliomas are investigated. Statistical studies applied on sets of metabolite concentrations and metabolite ratios extracted from 52 high resolu…
Effects of leflunomide (HWA 486) on expression of lymphocyte activation markers
1993
Leflunomide (HWA 486), an isoxazol derivative, has been shown to be very effective in combating autoimmune diseases and transplantation rejection in a great number of animal models. The main metabolite of leflunomide, A77 1726, is a potent antiproliferative compound. To further elucidate this effect, lymphocytes of healthy human donors were cultured for 24, 48 or 72 h in the presence of PHA or immobilized anti-CD3 antibody. A77 1726 was added at concentrations between 10 and 100 microM. Flow cytometric evaluation of early activation or proliferation markers (IL-2 and transferrin receptors, respectively) showed that their expression was inhibited in a dose-dependent manner by A77 1726. Toget…