Meeting report of the 4th European biotransformation workshop.

1. Challenges, strategies and new technologies in the field of biotransformation were presented and discussed at the fourth European Biotransformation Workshop which was held in collaboration with the joint ISSX/DMDG meeting on June 15, 2023 at the University of Hertfordshire in Hatfield, UK.2. In this meeting report we summarise the presentations and discussions from this workshop.3. The topics covered are listed below: Unusual biotransformation reactionsBiotransformation Workflows in Discovery utilising various softwares for structure elucidationBiotransformation software for the identification of peptide metabolitesAccelerator Mass Spectrometry (AMS) for endogenous and xenobiotic metabolite profilingMetabolite profiling using quantitative Nuclear magnetic resonance (NMR) and liquid chromatography coupled to inductively coupled plasma-mass spectrometry (LC-ICP-MS).

Meeting report of the second European biotransformation workshop.

Challenges and opportunities in the field of biotransformation were presented and discussed at the 2nd European Biotransformation workshop which was conducted virtually in collaboration with the DMDG on November 24/25, 2021. Here we summarise the presentations and discussions from this workshop.The following topics were covered:Regulatory requirements and biotransformation studies for antibody drug conjugates (ADCs) and antisense oligonucleotides (ASOs).Solutions for mass spectral data processing of peptides and oligonucleotides.Future outsourcing needs in biotransformation for new modalities.Established quantitative and qualitative workflows for metabolite identification.New in vitro systems to study new chemical entities (NCEs) with low metabolic turnover.New strategies on the timing of the human ADME (absorption, distribution, metabolism, excretion) study and to investigate the impact of human microbiome on drug development.

Meeting report of the first European biotransformation workshop.

1. Challenges and opportunities in the field of biotransformation were presented and discussed at the 1st European Biotransformation workshop which was conducted virtually in collaboration with the DMDG 27 January 2021. Here we summarize the presentations and discussions from this workshop.The following topics were covered:2. Needs for radiolabel for IND filing versus quantitation without standards.3. Applications of cyclic ion mobility in the field of biotransformation.4. Computational predictions of xenobiotic metabolism.5. Future (outsourcing) needs in biotransformation.6. Genotoxicity risk assessment of metabolites and qualification of impurities using metabolite data.7. Regulatory aspects of MIST.

Magnetic resonance imaging in pancreatitis.

Pancreatitis can occur in acute and chronic forms. Magnetic resonance imaging (MRI) plays an important role in the early diagnosis of both conditions and complications that may arise from acute or chronic inflammation of the gland. Standard MRI techniques including T1-weighted and T2-weighted fat-suppressed imaging sequences together with contrast-enhanced imaging can both aid in the diagnosis of acute pancreatitis and demonstrate complications as pseudocysts, hemorrhage, and necrosis. Combined use of MRI and MR cholangiopancreatography can show both parenchymal findings that are associated with chronic pancreatitis including pancreatic size and signal and arterial enhancements, all of which are diminished in chronic pancreatitis. The degree of main pancreatic duct dilatation and/or the number of side branch ectasia determines the diagnosis of chronic pancreatitis and its severity. In this paper, we report the spectrum of imaging findings of acute and chronic pancreatitis on MRI and MR cholangiopancreatography.

Serial contrast-enhanced MRI of the pancreas: correlation with secretin-stimulated endoscopic pancreatic function test.

RATIONALE AND OBJECTIVES: The purpose of this study was to determine the relationship between the pancreatic enhancement on serial contrast-enhanced MRI (CEMRI) and pancreatic exocrine function using the secretin-stimulated endoscopic pancreatic function test (ePFT). MATERIALS AND METHODS: A total of 30 patients with clinical symptoms consistent with chronic pancreatitis underwent CEMRI of the abdomen and ePFT within a 1- to 4-week interval. CEMRI was performed in arterial, early venous, and late venous phases. Secretin ePFT was performed with the measurement of HCO(3) concentration from the duodenal aspirates after secretin stimulation. Contrast enhancement ratio of the arterial phase to early venous phase was measured on CEMRI (SIRa/SIRv). A three-point evaluation system was used for grading the HCO(3) concentration and the enhancement ratio on MRI. For the significance of correlation, kappa statistics was used. Sensitivity and specificity of CEMRI was determined for the diagnosis of early chronic pancreatitis accepting ePFT as a reference. RESULTS: Twenty patients had identical scores on both secretin ePFT and CEMRI. Ten patients revealed discrepancy in scores. Kappa statistics revealed moderate agreement between MRI and ePFT (kappa = 0.44). Sensitivity and specificity values for the diagnosis of pancreatitis were 82% and 57%, respectively. Positive predictive value was 56%, and negative predictive value was 86%. CONCLUSION: The results of our data indicate that serial CEMRI is an appropriate imaging technique to rule out early chronic pancreatitis. However, secretin-stimulated imaging or ePFT may still be needed for the definite diagnosis of pancreatic exocrine dysfunction.

Studies on synthetic approaches to 1H- and 2H-indazolyl derivatives.

Synthetic approaches designed to provide 1H- and 2H-indazolyl derivatives of potential biological interest are reported. Special emphasis has been placed on the characterization of indazolylpyridinium products generated from reactions between indazole and 4-chloro-1-methylpyridinium iodide under various conditions. A stable mixture consisting of 3 parts of the 1H-isomer 9 to 1 part of the 2H-isomer 10 was obtained at room temperature in the presence of the base 2,2,6,6-tetramethylpiperidine (TMP). The same reaction at 60 degrees C gave only the 1H-isomer 9. At 100 degrees C in the absence of TMP only the 2H-isomer 10 was formed. The isomerization of 10 to 9 was found to proceed quantitatively at 60 degrees C but only in the presence of TMP. The effects of temperature and base on the course of these reactions are rationalized in terms of kinetic and thermodynamic parameters.

Video-assisted thoracic surgery for the management of pleural and pericardial effusion in Behçet's syndrome.

A 28-year-old man, who presented with pleural and pericardial chylous effusion secondary to superior vena cava syndrome, was diagnosed with Behcet's syndrome. A pericardial window was created by video-assisted thoracic surgery to relieve cardiac tamponade, and this technique also enabled lung biopsy, pleural abrasion, and drainage of the pleural effusion. We report this case because of its rarity. To the best of our knowledge, the literature contains no other report of the use of video-assisted thoracic surgery for creating a pericardial window for the treatment of cardiac tamponade in a case of Behcet's syndrome.

Primary vascular echinococcosis: an uncommon cause of chronic iliofemoral arterial occlusion.

We report the case of a 33-year-old woman who was admitted to our clinic with the diagnosis of chronic arterial occlusion of the right lower extremity. Preoperative angiography suggested an iliofemoral atherosclerotic occlusion. During surgery multiple hydatid cysts causing iliofemoral occlusion were found and excised. Arterial reconstruction was performed using an iliofemoral bypass technique with a polytetrafluoroethylene vascular graft. This case emphasizes that, in sheep-raising countries or in patients from such countries, primary vascular echinococcosis should be considered in the differential diagnosis of chronic arterial occlusion.

Traumatic tricuspid insufficiency following blunt chest trauma.

The insufficiency of the tricuspid valve developed due to blunt chest trauma is a rare and an insidiously progressing clinical incident. In this article we present a case which showed tricuspid insufficiency because of the rupture of the anterior papillary muscle due to trauma and which was treated surgically.