Determination of two phototransformation products of bentazone using quadrupole time-of-flight mass spectrometry

8 pages, 4 figures, 1 table.-- PMID: 17541562 [PubMed].-- Printed version published Jul 2007.The transformation products 2-isopropylcarbamoyl) phenylsulfamic acid and 2-(1-hydroxypropane-2-yl)-1,2-dihydroindazol-3-one could be determined during the photolysis of the herbicide bentazone. Degradation experiments were carried out with different types of water in a natural sunlight simulating system. Besides the anticipated hydroxylated bentazone, the second transformation product was identified by means of exact mass measurement using ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC/QqToF MS). Both phototransformation products occurred in all water types tested. The required irradiation time was matrix dependent. 2-(Isopropylcarbamoyl)phenylsulfamic acid was detected in a drainage channel in the Ebro river delta (Catalonia, Spain).This research project was funded by the European Union under the Global Change and Ecosystems (FP6) Water Cycle and Soil Related Aspects (AQUATERRA, Project number 505428 GOCE). Financial support from the Spanish Ministry of Education and Science (Project number CTM2005- 25168-E) is also acknowledged.Peer reviewe

Liver transplantation in glycogen storage disease type Ib: The role of SGLT2 inhibitors

We report on liver transplantation in two patients with GSD Ib on treatment with empagliflozin. The use of this SGLT2 inhibitor resulted in a marked decrease of 1,5-anhydroglucitol which has an important role in the development of neutropenia in this condition. As intended, this caused a significant rise of neutrophil numbers. Liver transplantation alone did not produce the desired effect and our observation argues for continuing SGLT2 inhibitor treatment after transplantation

Disturbed lipid and amino acid metabolisms in COVID-19 patients.

The Coronavirus disease 2019 (COVID-19) pandemic is overwhelming the healthcare systems. Identification of systemic reactions underlying COVID-19 will lead to new biomarkers and therapeutic targets for monitoring and early intervention in this viral infection. We performed targeted metabolomics covering up to 630 metabolites within several key metabolic pathways in plasma samples of 20 hospitalized COVID-19 patients and 37 matched controls. Plasma metabolic signatures specifically differentiated severe COVID-19 from control patients. The identified metabolic signatures indicated distinct alterations in both lipid and amino acid metabolisms in COVID-19 compared to control patient plasma. Systems biology-based analyses identified sphingolipid, tryptophan, tyrosine, glutamine, arginine, and arachidonic acid metabolism as mostly impacted pathways in COVID-19 patients. Notably, gamma-aminobutyric acid (GABA) was significantly reduced in COVID-19 patients and GABA plasma levels allowed for stratification of COVID-19 patients with high sensitivity and specificity. The data reveal large metabolic disturbances in COVID-19 patients and suggest use of GABA as potential biomarker and therapeutic target for the infection

Microbiota-derived 3-IAA influences chemotherapy efficacy in pancreatic cancer

Pancreatic ductal adenocarcinoma (PDAC) is expected to be the second most deadly cancer by 2040, owing to the high incidence of metastatic disease and limited responses to treatment. Less than half of all patients respond to the primary treatment for PDAC, chemotherapy, and genetic alterations alone cannot explain this. Diet is an environmental factor that can influence the response to therapies, but its role in PDAC is unclear. Here, using shotgun metagenomic sequencing and metabolomic screening, we show that the microbiota-derived tryptophan metabolite indole-3-acetic acid (3-IAA) is enriched in patients who respond to treatment. Faecal microbiota transplantation, short-term dietary manipulation of tryptophan and oral 3-IAA administration increase the efficacy of chemotherapy in humanized gnotobiotic mouse models of PDAC. Using a combination of loss- and gain-of-function experiments, we show that the efficacy of 3-IAA and chemotherapy is licensed by neutrophil-derived myeloperoxidase. Myeloperoxidase oxidizes 3-IAA, which in combination with chemotherapy induces a downregulation of the reactive oxygen species (ROS)-degrading enzymes glutathione peroxidase 3 and glutathione peroxidase 7. All of this results in the accumulation of ROS and the downregulation of autophagy in cancer cells, which compromises their metabolic fitness and, ultimately, their proliferation. In humans, we observed a significant correlation between the levels of 3-IAA and the efficacy of therapy in two independent PDAC cohorts. In summary, we identify a microbiota-derived metabolite that has clinical implications in the treatment of PDAC, and provide a motivation for considering nutritional interventions during the treatment of patients with cancer.</p